Mouse Adrenal Chromaffin Cell Isolation

Adrenal medullary chromaffin cell culture systems are extremely useful for the study of excitation-secretion coupling in an in vitro setting.  This ...

growth-factor-coated-bead-placement-on-dorsal-forebrain-explants

Growth Factor-Coated Bead Placement on Dorsal Forebrain Explants

Mouse Dorsal Forebrain Explant Isolation

culture-of-mouse-neural-stem-cell-precursors

Culture of Mouse Neural Stem Cell Precursors

Primary neural stem cell cultures are useful for studying the mechanisms underlying central nervous system development. Stem cell research will increase ...

June 2012: This Month in JoVE

Back in 1905, in what is now the Czech Republic, Eduard Zirm performed the first corneal transplantation surgery (keratoplasty), which restored vision to ...

July 2012: This Month in JoVE

Historically, JoVE, The Journal of Visualized Experiments, has focused primarily on biomedical research and has developed subsections for Bioengineering, ...

August 2012: This Month in JoVE

Traditional microscopy requires lens objectives to magnify specimens, and can involve numerous optical components like additional objectives, filters, and ...

September 2012: This Month in JoVE

This September in JoVE, researchers from the School of Medicine at the Free University of Berlin demonstrate a novel method for studying how stroke ...

October 2012: This Month in JoVE

Here are some highlights from the October 2012 issue of Journal of Visualized Experiments (JoVE).  Gr&oslash;nlund et al. demonstrate how to isolate and ...

November 2012: This Month in JoVE

In this issue, Oestreicher et al. show us how to isolate magnetotactic bacteria from freshwater samples, and concentrate the bacteria at one end of a ...

December 2012: This Month in JoVE

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2012: A Year In Review

 
 
Here's a look at some of the milestones and highlights of the year 2012 in Journal of Visualized Experiments (JoVE).
At the start of 2012, JoVE ...

February 2013: This Month in JoVE

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Since JoVE's first issue, biomedical research ...

March 2013: This Month in JoVE

Here are some highlights from the March 2013 issue of Journal of Visualized Experiments (JoVE).
This month, JoVE features several video articles in the ...

September 2013 - This Month in JoVE

Here's a look at what's coming up in the September 2013 issue of JoVE: The Journal of Visualized Experiments.
Palatogenesis (palate formation) involves ...

October 2013 - This Month in JoVE

Here's a look at what's coming up in the October 2013 issue of JoVE (The Journal of Visualized Experiments).
This month we are pleased to introduce JoVE ...

November 2013: This Month in JoVE

Here's a look at what's coming up in the November 2013 issue of JoVE: The Journal of Visualized Experiments.
In the biomedical sciences, many principles ...

December 2013: This Month in JoVE

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This holiday season, we bring you techniques ...

JoVE 2013: The Year in Review

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January featured ...

February 2014: This Month in JoVE

Here's a look at what's coming up in the February 2014 issue of JoVE: The Journal of Visualized Experiments.
This month, we have an improved method for ...

march-2014-this-month-jove-food-related-motivation-pathogens-deli

March 2014: This Month in JoVE - Food-Related Motivation, Pathogens in the Deli, Diagnosing ALS, and Bioengineering Cells into Patterns

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This month, we have a special culinary focus ...

april-2014-this-month-jove-bioengineering-for-acl-tears-neuroscience

April 2014: This Month in JoVE - Bioengineering for ACL Tears, Neuroscience behind Insect Locomotion, Improved Genetic Engineering of Crops, and Synthesizing Secret Ink

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In the Bioengineering section we have a video ...

may-2014-this-month-jove-bioengineering-limb-prostheses-protecting

May 2014: This Month in JoVE - Bioengineering Limb Prostheses, Protecting Trees from Fungal Pathogens, and Investigating the Kinematics of Swallowing

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In JoVE Environment we examine beech bark disease, ...

june-2014-this-month-jove-3d-virtual-navigation-human-brain

June 2014: This Month in JoVE - 3D Virtual Navigation in the Human Brain, Simulation of Planet Formation, and Bioprinting Cultured Cartilage Grafts

Here's a look at what's coming up in the June 2014 issue of JoVE: The Journal of Visualized Experiments.
The human brain has been called the next frontier ...

july-2014-this-month-jove-shrinkage-stress-dental-fillings-olfactory

July 2014: This Month in JoVE - Shrinkage Stress in Dental Fillings, Olfactory Learning in Honeybees, Age-related Balance Changes, and Chemical Distribution in the Environment

Here's a look at what's coming up in the July 2014 issue of JoVE: The Journal of Visualized Experiments.
Going to the dentist to get a cavity filled is ...

august-2014-this-month-jove-chemical-sensing-robots-tracking-blood

August 2014: This Month in JoVE - Chemical Sensing Robots, Tracking Blood Cell Development, Rodents on the Treadmill, and Simulating Urban Runoff

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The ability to detect scent is the most ...

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September 2014: This Month in JoVE - Visualizing Coral, Injecting Hydra, Engineering Corneal Implants, and Assessing Traumatic Brain injury in Children

Here's a look at what's coming up in the September 2014 issue of JoVE: The Journal of Visualized Experiments.
As summer comes to an end in the Earth's ...

october-2014-this-month-jove-visualizing-infectious-disease

October 2014: This Month in JoVE - Visualizing Infectious Disease, Transfecting with the Gene Gun, and a Novel Bioreactor System

Here's a look at what's coming up in the October 2014 issue of JoVE: The Journal of Visualized Experiments.
Right now, the world is witnessing the worst ...

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November 2014: This Month in JoVE: Flow Cytometry in Space, Venom Extraction from Spiders, Decision Making in Bumblebees, and Oceanic Microbial Communities

Here's a look at what's coming up in the November 2014 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Biology, we have a lot of videos that ...

December 2014: JoVE's Year in Review

In this Year in Review, we showcase some of our favorite video articles of the year 2014 in JoVE: The Journal of Visualized Experiments.
In January, JoVE ...

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January 2015: This Month in JoVE - Introducing JoVE Developmental Biology

Here's a look at what's coming up in the January 2015 issue of JoVE: The Journal of Visualized Experiments.
JoVE has been revolutionizing scientific ...

february-2015-this-month-jove-tracking-down-foodborne-illness-imaging

February 2015: This Month in JoVE - Tracking Down Foodborne Illness, Imaging Baby Brains, and Paying Scientific Attention to Attention

Here's a look at what's coming up in the February 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Environment we have a method for ...

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March 2015: This Month in JoVE - Solving Crime with Science, Applying Technology to Understand Trees, and Studying Protein Synthesis on a Chip

Here's a look at what's coming up in the March 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Environment, we really love ...

april-2015-this-month-jove-studying-locomotion-drunken-worms

April 2015: This Month in JoVE - Studying Locomotion in Drunken Worms, Preserving Human Liver for Transplantation, and Visualizing Bacterial Swarms

Here's a look at what's coming up in the April 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Neuroscience, it is clear that alcohol ...

this-month-jove-assessing-freezing-tolerance-plants-patterning-2d

This Month in JoVE - Assessing Freezing Tolerance in Plants, Patterning 2D Shapes with DNA, Studying Ischemia <em>In Vitro</em>, Studying Social Cognition in Monkeys

Here's a look at what's coming up in the May 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Environment, it's the middle of spring in ...

june-2015-this-month-in-jove-celebrating-jove-s-100th-issue

June 2015: This Month in JoVE - Celebrating JoVE's 100th Issue

Here's a look at what's coming up in the June 2015 issue of JoVE: The Journal of Visualized Experiments.
This month marks the release of JoVE's 100th ...

july-2015-this-month-jove-treating-canine-halitosis-minimizing

July 2015 - This Month in JoVE: Treating Canine Halitosis, Minimizing Workplace Stress, and Assessing Electrical Activity and Herbicide Resistance in Plants

Here's a look at what's coming up in the July 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Medicine, we feature an approach for ...

august-2015-this-month-jove-isolating-stem-cells-bioengineering

August 2015 - This Month in JoVE: Isolating Stem Cells, Bioengineering the Kidney, and Getting Kids to eat Carrots

Here's a look at what's coming up in the August 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Developmental Biology, a major goal in ...

september-2015-this-month-jove-measuring-greenhouse-gases-herbicide

September 2015 - This Month in JoVE: Measuring Greenhouse Gases and Herbicide Resistance, Bioengineering Bone, and Analyzing Neuromuscular Control with Virtual Reality

Here's a look at what's coming up in the September 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Environment, we've had a pretty warm ...

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October 2015 - This Month in JoVE: tuberculosis infection modeling, telemetric temperature pills, bioengineered cartilage, and 3D neuronal networks

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In JoVE Immunology &amp; Infection, we feature ...

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November 2015 - This Month in JoVE: Drosophila Social Space, Structured Rehabilitation for Multifunctional Prosthetics, and Thermal Imaging in Wild Birds

Here's a look at what's coming up in the November 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Neuroscience, we know that fruit ...

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December 2015 - This Month in JoVE: Flu Surveillance in Swine, DNA Nanorobots, Analyzing Crude Oil, and a Translational Model of Depression

Here's a look at what's coming up in the December 2015 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Immunology &amp; Infection, we know ...

JoVE - Year in Review: 2015

In January 2015, JoVE Developmental Biology became the newest addition to the JoVE family, and featured a live-imaging protocol for visualizing the ...

february-2016-this-month-jove-photoconvertible-proteins-gold

February 2016 - This Month in JoVE: Photoconvertible Proteins, Gold Nanoparticles, PET Principles, and Bone Marrow Microenvironments

Here's a look at what's coming up in the February 2016 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Developmental Biology, the ...

march-2016-this-month-jove-rna-interference-mosquitoes-ipscs-derived

March 2016 - This Month in JoVE: RNA interference in Mosquitoes, iPSCs Derived from Nasal Epithelia, Air Sampling of Atmospheric Aerosols, and Autologous Micro-grafts for Skin Lesions

Here's a look at what's coming up in the March 2016 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Biology, RNA interference (RNAi) is a ...

april-2016-this-month-jove-cell-migration-bacterial-motility

April 2016 - This Month in JoVE: Cell Migration, Bacterial Motility, Psycholinguistics, and In Vitro Eye Model for Contact Lenses

Here's a look at what's coming up in the April 2016 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Developmental Biology, cell migration is ...

may-2016-this-month-jove-cheetah-footprints-lens-stiffness-digitally

May 2016 - This Month in JoVE: Cheetah footprints, lens stiffness, and digitally printed solar cells

Here's a look at what's coming up in the May 2016 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Environment, we examine the cheetah-one of ...

june-2016-this-month-jove-blueberry-analysis-impact-testing-football

June 2016 - This Month in JoVE: Blueberry Analysis, Impact Testing Football Helmets, Stencil Micropatterning of Stem Cells, and a Test for Soil Plasticity

Here's a look at what's coming up in the June 2016 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Chemistry, just in time for blueberry ...

July 2016: This Month in JoVE

Here's a look at what's coming up in the July 2016 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Neuroscience, gustatory perception - or ...

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August 2016 - This Month in JoVE: Sampling in Suspension Feeders, Staining Three-Dimensional Skin, Spasms in the Heart Vasculature, and Emotional Reponses to Beverages

Here's a look at what's coming up in the August 2016 issue of JoVE: The Journal of Visualized Experiments.
In JoVE Environment, we take a look at aquatic ...

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September 2016-This Month in JoVE: Introducing JoVE Genetics, JoVE Biochemistry, and JoVE Cancer Research

This month we are pleased to introduce three new sections of the JoVE family: Genetics, Biochemistry, and Cancer Research.
JoVE Genetics contains ...

October 2016: This Month in JoVE

Here's a look at what's coming up in the October 2016 issue of JoVE: The Journal of Visualized Experiments.
In Immunology and Infection, we showcase a ...

november-2016-this-month-jove-turtle-tracking-acids-coffee-squid

November 2016 - This Month in JoVE: Turtle tracking, acids in coffee, squid coloration and glucose tolerance in primates

Here's a look at what's coming up in the November 2016 issue of JoVE: The Journal of Visualized Experiments.
Think you're good at navigation? How about if ...

December 2016: This Month in JoVE

Here's a look at what's coming up in the December 2016 issue of JoVE: The Journal of Visualized Experiments.
Grant deadlines, training interns, and ...

2016: This Year in JoVE

Welcome to JoVE's Year in Review, where we highlight some of the most interesting video protocols of the past year.
In January 2016 JoVE started out with ...

JoVE Monthly Highlights: February 2017

Here's a look at what's coming up in the February 2017 issue of JoVE: The Journal of Visualized Experiments.
After a long day at the bench, who doesn't ...

JoVE Monthly Highlights: March 2017

Here's a look at what's coming up in the March 2017 issue of JoVE: The Journal of Visualized Experiments.
As the start of spring brings new life, we begin ...

JoVE Monthly Highlights: April 2017

Here's a look at what's coming up in the April 2017 issue of JoVE: The World's Premier Video Journal 
The plight of the honeybee holds our first spotlight ...

JoVE Monthly Highlights: May 2017

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Mindfulness is at the heart of our first featured ...

JoVE Monthly Highlights: June 2017

Here's a look at what's coming up in the June 2017 issue of JoVE: The World's Premier Video Journal
A "handy" method to test the efficacy of sanitizing ...

An Introduction to Neuroanatomy

Neuroanatomy is the study of nervous system structures and how they relate to function. One focus of neuroanatomists is the macroscopic structures within ...

July 2013: This Month in JoVE

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This month, we take a dip in the zebrafish tank ...

June 2013: This Month in JoVE

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Since JoVE first launched in 2006, we have ...

May 2013: This Month in JoVE

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What came first: the chicken or the egg? This ...

April 2013: This Month in JoVE

Here's a look at what's coming up in the April 2013 issue of Journal of Visualized Experiments (JoVE).
It's usually not permissible to have food in ...

August 2013: This Month in JoVE

Here&#8217;s a look at what&#8217;s coming up in the August 2013 issue of JoVE: The Journal of Visualized Experiments.
Honey is an age-old anti-aging ...

University of California, Irvine (UCI)

JoVE Content Production

TODO

&#x5C0F;&#x7535;&#x5BFC; Ca2 +-&#x6FC0;&#x6D3B;&#x7684; K + &#x6E20;&#x9053;&#xFF0C;&#x4EA7;&#x54C1; sk1 &#x7EC4;&#x5408;&#x6210; SK3 &#x57FA;&#x56E0;&#xFF0C;&#x8C03;&#x8282;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x5185;&#x5916;&#x819C;&#x5174;&#x594B;&#x6027;&#x3002;&#x6211;&#x4EEC;&#x62A5;&#x544A; SK3 variant (SK3-1 C)&#xFF0C;&#x4E0D;&#x540C;&#x4E8E; SK3 &#x5229;&#x7528;&#x5916;&#x663E;&#x66FF;&#x4EE3;&#x7B2C;&#x4E00;&#x5B50; (&#x5916;&#x663E;&#x5B50; 1 C&#xFF09; &#x4EE3;&#x66FF; SK3&#xFF0C;&#x6240;&#x7528;&#x7684;&#x5916;&#x663E;&#x5B50; 1A &#x4F46;&#x5426;&#x5219;&#x7B49;&#x540C;&#x4E8E; SK3 &#x7684;&#x8868;&#x5F81;&#x3002;&#x5B9A;&#x91CF;&#x9006;&#x8F6C;&#x5F55;-&#x805A;&#x5408;&#x9176;&#x94FE;&#x53CD;&#x5E94;&#x5728;&#x4EBA;&#x4F53;&#x7684;&#x6DCB;&#x5DF4;&#x7EC4;&#x7EC7;&#x3001; &#x9AA8;&#x9ABC;&#x808C;&#x3001; &#x6C14;&#x7BA1;&#xFF0C;&#x548C;&#x6D8E;&#x817A;&#x4F46;&#x4E0D;&#x662F;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x4E2D;&#x68C0;&#x6D4B;&#x5230;&#x4E30;&#x5BCC;&#x8868;&#x8FBE;&#x7684; SK3-1 C &#x6210;&#x7EE9;&#x5355;&#x3002;SK3-1 C &#x4E0D;&#x4EA7;&#x751F;&#x529F;&#x80FD;&#x9891;&#x9053;&#x65F6;&#x72EC;&#x81EA;&#x5728;&#x54FA;&#x4E73;&#x52A8;&#x7269;&#x7EC6;&#x80DE;&#x4E2D;&#x8868;&#x8FBE;&#xFF0C;&#x4F46;&#x9690;&#x542B; sk1 &#x7EC4;&#x5408;&#x6210;&#x3001; SK2&#x3001; SK3 &#x548C; IKCa1 &#x7684;&#x6E20;&#x9053;&#xFF0C;&#x4F46;&#x4E0D;&#x662F;&#x94BE;&#x6216; KV &#x901A;&#x9053;&#x3002;&#x5171;&#x805A;&#x7126;&#x663E;&#x5FAE;&#x955C;&#x53D1;&#x73B0; SK3-1 C &#x819C;&#x5C42;&#x56FA; SK3 &#x86CB;&#x767D;&#x8D28;&#x3002;&#x663E;&#x6027;&#x6291;&#x5236;&#x6D3B;&#x6027;&#x7684; SK3-1 C &#x6CA1;&#x6709;&#x975E;&#x7279;&#x5F02;&#x6027;&#x9499;&#x8C03;&#x86CB;&#x767D;&#x6D77;&#x7EF5;&#x6548;&#x5E94;&#x56E0;&#x4E3A;&#x9499;&#x8C03;&#x7D20;&#x7684;&#x8868;&#x8FBE;&#x5E76;&#x6CA1;&#x6709;&#x51FA;&#x73B0;&#x9006;&#x8F6C; SK3 &#x86CB;&#x767D;&#x8D28;&#x548C;&#x9499;&#x8C03;&#x86CB;&#x767D;&#x4ECB;&#x5BFC; SK3 1 C &#x80DE;&#x5185;&#x7684;&#x9677;&#x5370;-Ca2 +-&#x4F9D;&#x8D56;&#x706D;&#x6D3B;&#x7684;&#x7EA4;&#x6E20;&#x9053;&#x5E76;&#x4E0D;&#x53D7; SK3-1 C &#x8FC7;&#x5EA6;&#x8868;&#x8FBE;&#x3002;&#x5220;&#x9664;&#x5206;&#x6790;&#x786E;&#x5B9A;&#x4E2D;&#x7684;&#x7C7B;&#x4F3C;&#x4E8E;&#x56DB;&#x805A;&#x87BA;&#x65CB;&#x76D8;&#x7ED5;&#x57DF;&#x62A5;&#x544A;&#x4EE5;&#x52A0;&#x5F3A;&#x56DB;&#x805A;&#x4F53;&#x7A33;&#x5B9A;&#x6027;&#x548C;&#x9009;&#x62E9;&#x6027;&#x7684;&#x6E20;&#x9053;&#x5F88;&#x591A; K + multimerization &#x7684; SK3-1 C C &#x603B;&#x7AD9;&#x7684;&#x663E;&#x6027;&#x6291;&#x5236;&#x90E8;&#x5206;&#x3002;SK3-1 C &#x53EF;&#x80FD;&#x56E0;&#x6B64;&#x6291;&#x5236;&#x9499;&#x8C03;&#x7D20;&#x95E8;&#x63A7; SKCa/IKCa &#x6E20;&#x9053;&#x901A;&#x8FC7;&#x6355;&#x83B7;&#x8FD9;&#x4E9B;&#x901A;&#x9053;&#x86CB;&#x767D;&#x8D28;&#x4E9A;&#x57FA;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x4ECB;&#x5BFC;&#x7684;&#x663E;&#x6027;&#x6291;&#x5236;&#x90E8;&#x5206;&#x901A;&#x8FC7;&#x819C;&#x5C42;&#xFF0C;&#x4ECE;&#x800C;&#x51CF;&#x5C11;&#x7EC6;&#x80DE;&#x8868;&#x9762;&#x529F;&#x80FD;&#x901A;&#x9053;&#x8868;&#x8FBE;&#x3002;&#x8FD9;&#x79CD;&#x5BB6;&#x5EAD;&#x5168;&#x663E;&#x6027;&#x8D1F;&#x5236;&#x6B62; SK3-1 C &#x63D0;&#x4F9B;&#x4E86;&#x529F;&#x80FD;&#x5F3A;&#x5927;&#x7684;&#x673A;&#x5236;&#xFF0C;&#x4EE5;&#x6EF4;&#x5B9A;&#x7EC6;&#x80DE;&#x819C;&#x5174;&#x594B;&#x6027;&#x548C;&#x662F;&#x901A;&#x8FC7;&#x5176;&#x6709;&#x9488;&#x5BF9;&#x6027;&#x5730;&#x6C89;&#x9ED8;&#x5728;&#x4E0D;&#x540C;&#x7EC4;&#x7EC7;&#x4E2D;&#x5B9A;&#x4E49;&#x8FD9;&#x4E9B;&#x901A;&#x9053;&#x7684;&#x529F;&#x80FD;&#x5728;&#x4F53;&#x5185;&#x4F5C;&#x7528;&#x7684;&#x6709;&#x76CA;&#x505A;&#x6CD5;&#x3002;

SK3-1 C&#x3001; &#x663E;&#x6027;&#x8D1F;&#x6291;&#x764C; SKCa &#x548C; IKCa &#x7684;&#x6E20;&#x9053;&#x3002;

Small conductance Ca2+-activated K+ channels, products of the SK1-SK3 genes, regulate membrane excitability both within and outside the nervous system. We report the characterization of a SK3 variant (SK3-1C) that differs from SK3 by utilizing an alternative first exon (exon 1C) in place of exon 1A used by SK3, but is otherwise identical to SK3. Quantitative RT-PCR detected abundant expression of SK3-1C transcripts in human lymphoid tissues, skeletal muscle, trachea, and salivary gland but not the nervous system. SK3-1C did not produce functional channels when expressed alone in mammalian cells, but suppressed SK1, SK2, SK3, and IKCa1 channels, but not BKCa or KV channels. Confocal microscopy revealed that SK3-1C sequestered SK3 protein intracellularly. Dominant-inhibitory activity of SK3-1C was not due to a nonspecific calmodulin sponge effect since overexpression of calmodulin did not reverse SK3-1C-mediated intracellular trapping of SK3 protein, and calmodulin-Ca2+-dependent inactivation of CaV channels was not affected by SK3-1C overexpression. Deletion analysis identified a dominant-inhibitory segment in the SK3-1C C terminus that resembles tetramerization-coiled-coiled domains reported to enhance tetramer stability and selectivity of multimerization of many K+ channels. SK3-1C may therefore suppress calmodulin-gated SKCa/IKCa channels by trapping these channel proteins intracellularly via subunit interactions mediated by the dominant-inhibitory segment and thereby reduce functional channel expression on the cell surface. Such family-wide dominant-negative suppression by SK3-1C provides a powerful mechanism to titrate membrane excitability and is a useful approach to define the functional in vivo role of these channels in diverse tissues by their targeted silencing.

SK3-1C, a dominant-negative suppressor of SKCa and IKCa channels.

Conductance Petit Ca2 + activ&#xE9;s par les canaux K +, produits des g&#xE8;nes SK1-SK3, r&#xE9;guler l&#x26;#39;excitabilit&#xE9; membranaire &#xE0; l&#x26;#39;int&#xE9;rieur et l&#x26;#39;ext&#xE9;rieur du syst&#xE8;me nerveux. Nous rapportons la caract&#xE9;risation d&#x26;#39;une variante SK3 (SK3-1C) qui diff&#xE8;re de SK3 en utilisant un exon premi&#xE8;re alternative (exon 1C) &#xE0; la place de l&#x26;#39;exon 1A utilis&#xE9; par SK3, mais est par ailleurs identique &#xE0; SK3. RT-PCR quantitative d&#xE9;tect&#xE9; l&#x26;#39;expression abondante de SK3-1C transcrits dans les tissus lympho&#xEF;des de l&#x26;#39;homme, le muscle squelettique, la trach&#xE9;e et glandes salivaires, mais pas le syst&#xE8;me nerveux. SK3-1C ne produisent pas de canaux fonctionnels lorsqu&#x26;#39;ils sont exprim&#xE9;s seuls dans des cellules de mammif&#xE8;res, mais supprim&#xE9;es SK1, SK2, SK3 et IKCa1 canaux, mais pas les canaux BKCa ou KV. La microscopie confocale a r&#xE9;v&#xE9;l&#xE9; que SK3-1C s&#xE9;questr&#xE9; SK3 prot&#xE9;ines intracellulaire. Dominant une activit&#xE9; inhibitrice de la SK3-1C n&#x26;#39;&#xE9;tait pas due &#xE0; un effet d&#x26;#39;&#xE9;ponge calmoduline non sp&#xE9;cifique depuis la surexpression de la calmoduline ne pas inverser SK3-1C-m&#xE9;diation pi&#xE9;geage intracellulaire de SK3 prot&#xE9;ines, et de la calmoduline-Ca 2 +-d&#xE9;pendante inactivation des canaux Cav n&#x26;#39;a pas &#xE9;t&#xE9; affect&#xE9;e par SK3 1C-surexpression. Suppression d&#x26;#39;analyse a identifi&#xE9; un segment dominant-inhibitrice dans le terminus SK3-1C C qui ressemble &#xE0; t&#xE9;tram&#xE9;risation-enroul&#xE9; &#xE0; spires domaines signal&#xE9;s pour am&#xE9;liorer la stabilit&#xE9; et la s&#xE9;lectivit&#xE9; t&#xE9;tram&#xE8;re de multim&#xE9;risation de nombreux canaux K +. SK3-1C peut donc supprimer la calmoduline-d&#xE9;pendants SKCA / IKCa canaux en pi&#xE9;geant ces prot&#xE9;ines canal intracellulaire par l&#x26;#39;interm&#xE9;diaire d&#x26;#39;interactions de sous-unit&#xE9;s &#xE0; m&#xE9;diation par le segment dominante inhibitrice et de r&#xE9;duire ainsi l&#x26;#39;expression du canal fonctionnel sur la surface cellulaire. Une telle famille &#xE0; l&#x26;#39;&#xE9;chelle dominante-n&#xE9;gative suppression par SK3-1C fournit un m&#xE9;canisme puissant pour titrer excitabilit&#xE9; de la membrane et est une approche utile pour d&#xE9;finir le r&#xF4;le in vivo fonctionnelle de ces canaux dans les tissus divers par leur silence cibl&#xE9;e.

SK3-1C, un suppresseur dominant n&#xE9;gatif de canaux SKCA et IKCa

SK3-1C, eine dominant-negative Suppressor of SKCa und IKCa Kan&#xE4;le.

Piccola conduttanza Ca2 +-attivazione canali K +, prodotti dei geni SK1-SK3, regolano l&#39;eccitabilit&agrave; di membrana sia all&#39;interno che all&#39;esterno del sistema nervoso. Riportiamo la caratterizzazione di una variante SK3 (SK3-1C) che si differenzia da SK3 utilizzando un esone alternativo (esone 1 C) al posto di esone 1A utilizzato da SK3, ma altrimenti &egrave; identico a SK3. RT-PCR quantitativo rilevato abbondanti espressione delle trascrizioni SK3-1 C nei tessuti linfoidi umani, muscolo scheletrico, trachea e delle ghiandole salivari, ma non il sistema nervoso. SK3-1 C non produrre canali funzionali quando espresse solo in cellule di mammifero, ma soppressa canali SK1, SK2, SK3 e IKCa1, ma non BKCa o KV canali. Microscopia confocale ha rivelato che SK3-1 C sequestrato SK3 proteina intracellularly. Attivit&agrave; dominante-inibitoria SK3-1C non era dovuto ad un effetto spugna calmodulina aspecifici poich&eacute; la sovraespressione della calmodulina non ha fatto retromarcia SK3-1 C-mediata trapping intracellulare della proteina SK3 e calmodulina-Ca2 +-dipendente dalla inattivazione dei canali del CaV non &egrave; stata influenzata da iperespressione SK3-1 C. Analisi di delezione individuato un segmento dominante-inibitorio in SK3-1 C C terminale che assomiglia a avvolto a spirale di tetramerization domini segnalati per migliorare la stabilit&agrave; del tetramero e selettivit&agrave; di multimerization di molti canali del K +. SK3-1 C pu&ograve; quindi sopprimere gated la calmodulina SKCa/IKCa canali intrappolando queste proteine canale intracellularly tramite interazioni di subunit&agrave; mediate dal segmento dominante-inibitorio e ridurre cos&igrave; espressione funzionale canale sulla superficie della cellula. Tale livello famiglia dominante-negativo soppressione da SK3-1 C fornisce un potente meccanismo per titolo eccitabilit&agrave; di membrana ed &egrave; un approccio utile a definire il ruolo funzionale in vivo di questi canali in tessuti diversi dal loro silenzio mirati.

SK3-1C, un soppressore di dominante negativo di canali SKCa e IKCa.

&#x5C0F;&#x30B3;&#x30F3;&#x30C0;&#x30AF;&#x30BF;&#x30F3;&#x30B9;&#x30AB;&#x30EB;&#x30B7;&#x30A6;&#x30E0;&#x6D3B;&#x6027;&#x5316;K +&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x3001;SK1-SK3&#x907A;&#x4F1D;&#x5B50;&#x306E;&#x7523;&#x7269;&#x306F;&#x3001;&#x795E;&#x7D4C;&#x7CFB;&#x5185;&#x3068;&#x5916;&#x3001;&#x4E21;&#x65B9;&#x306E;&#x819C;&#x8208;&#x596E;&#x6027;&#x3092;&#x8ABF;&#x7BC0;&#x3059;&#x308B;&#x3002;&#x79C1;&#x305F;&#x3061;&#x306F;&#x3001;SK3&#x3067;&#x4F7F;&#x7528;&#x3055;&#x308C;&#x308B;&#x30A8;&#x30AF;&#x30BD;&#x30F3;1A&#x306E;&#x4EE3;&#x308F;&#x308A;&#x306B;&#x5225;&#x306E;&#x7B2C;&#x4E00;&#x30A8;&#x30AF;&#x30BD;&#x30F3;&#xFF08;&#x30A8;&#x30AF;&#x30BD;&#x30F3;1C&#xFF09;&#x3092;&#x5229;&#x7528;&#x3057;&#x3066;SK3&#x7570;&#x306A;&#x308A;SK3&#x5909;&#x7570;&#x4F53;&#xFF08;SK3-1C&#xFF09;&#x306E;&#x7279;&#x6027;&#x3092;&#x5831;&#x544A;&#x3057;&#x305F;&#x304C;&#x3001;SK3&#x306B;&#x305D;&#x3046;&#x3067;&#x306A;&#x3044;&#x5834;&#x5408;&#x3068;&#x540C;&#x3058;&#x3067;&#x3059;&#x3002;&#x5B9A;&#x91CF;&#x7684;RT-PCR&#x306F;SK3-1C&#x4EBA;&#x9593;&#x306E;&#x30EA;&#x30F3;&#x30D1;&#x7D44;&#x7E54;&#x306B;&#x304A;&#x3051;&#x308B;&#x8EE2;&#x5199;&#x3001;&#x9AA8;&#x683C;&#x7B4B;&#x3001;&#x6C17;&#x7BA1;&#x3001;&#x553E;&#x6DB2;&#x817A;&#x3067;&#x306F;&#x306A;&#x304F;&#x3001;&#x795E;&#x7D4C;&#x7CFB;&#x306E;&#x5927;&#x91CF;&#x767A;&#x73FE;&#x3092;&#x691C;&#x51FA;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002; SK3-1C&#x306F;&#x3001;&#x6A5F;&#x80FD;&#x7684;&#x54FA;&#x4E73;&#x52D5;&#x7269;&#x7D30;&#x80DE;&#x5185;&#x3067;&#x5358;&#x72EC;&#x3067;&#x767A;&#x73FE;&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x304C;&#x3001;&#x6291;&#x5236;SK1&#x3001;SK2&#x3001;SK3&#x3001;&#x3068;IKCa1&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x3067;&#x306F;&#x306A;&#x304F;&#x3001;BKCa&#x307E;&#x305F;&#x306F;KV&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x3092;&#x751F;&#x6210;&#x3057;&#x307E;&#x305B;&#x3093;&#x3067;&#x3057;&#x305F;&#x3002;&#x5171;&#x7126;&#x70B9;&#x9855;&#x5FAE;&#x93E1;&#x306F;&#x3001;SK3-1C&#x306F;&#x3001;&#x7D30;&#x80DE;&#x5185;SK3&#x86CB;&#x767D;&#x8CEA;&#x3092;&#x9694;&#x96E2;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x305F;&#x3002; SK3-1C&#x306E;&#x30C9;&#x30DF;&#x30CA;&#x30F3;&#x30C8;&#x963B;&#x5BB3;&#x6D3B;&#x6027;&#x306F;&#x30AB;&#x30EB;&#x30E2;&#x30B8;&#x30E5;&#x30EA;&#x30F3;&#x306E;&#x904E;&#x5270;&#x767A;&#x73FE;&#x306F;SK3&#x86CB;&#x767D;&#x8CEA;&#x306E;SK3-1C-&#x4ECB;&#x5728;&#x7D30;&#x80DE;&#x30C8;&#x30E9;&#x30C3;&#x30D7;&#x3092;&#x9006;&#x306B;&#x3057;&#x306A;&#x304B;&#x3063;&#x305F;&#x3057;&#x3001;CAV&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306E;&#x30AB;&#x30EB;&#x30E2;&#x30B8;&#x30E5;&#x30EA;&#x30F3;&#x306E;Ca2 +&#x4F9D;&#x5B58;&#x6027;&#x306E;&#x4E0D;&#x6D3B;&#x5316;&#x306F;SK3&#x306E;&#x5F71;&#x97FF;&#x3092;&#x53D7;&#x3051;&#x306A;&#x304B;&#x3063;&#x305F;&#x306E;&#x3067;&#x3001;&#x975E;&#x7279;&#x7570;&#x7684;&#x30AB;&#x30EB;&#x30E2;&#x30B8;&#x30E5;&#x30EA;&#x30F3;&#x30B9;&#x30DD;&#x30F3;&#x30B8;&#x52B9;&#x679C;&#x306B;&#x3088;&#x308B;&#x3082;&#x306E;&#x3067;&#x306F;&#x306A;&#x304B;&#x3063;&#x305F;-1C&#x904E;&#x5270;&#x767A;&#x73FE;&#x3002;&#x6B20;&#x5931;&#x89E3;&#x6790;&#x306F;&#x3001;&#x591A;&#x304F;&#x306E;K +&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306E;&#x591A;&#x91CF;&#x4F53;&#x306E;&#x56DB;&#x91CF;&#x4F53;&#x306E;&#x5B89;&#x5B9A;&#x6027;&#x3068;&#x9078;&#x629E;&#x6027;&#x3092;&#x9AD8;&#x3081;&#x308B;&#x3053;&#x3068;&#x304C;&#x5831;&#x544A;&#x56DB;&#x91CF;&#x4F53;&#x3001;&#x30B3;&#x30A4;&#x30EB;&#x30C9;&#x30B3;&#x30A4;&#x30EB;&#x30C9;&#x30E1;&#x30A4;&#x30F3;&#x306B;&#x4F3C;&#x3066;&#x3044;&#x308B;SK3-1C C&#x672B;&#x7AEF;&#x306B;&#x652F;&#x914D;&#x7684;&#x306A;&#x963B;&#x5BB3;&#x30BB;&#x30B0;&#x30E1;&#x30F3;&#x30C8;&#x3092;&#x540C;&#x5B9A;&#x3057;&#x305F;&#x3002; SK3-1C&#x3057;&#x305F;&#x304C;&#x3063;&#x3066;&#x3001;&#x652F;&#x914D;&#x7684;&#x306A;&#x963B;&#x5BB3;&#x30BB;&#x30B0;&#x30E1;&#x30F3;&#x30C8;&#x306B;&#x3088;&#x3063;&#x3066;&#x5A92;&#x4ECB;&#x3055;&#x308C;&#x308B;&#x30B5;&#x30D6;&#x30E6;&#x30CB;&#x30C3;&#x30C8;&#x306E;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x3092;&#x4ECB;&#x3057;&#x3066;&#x7D30;&#x80DE;&#x5185;&#x3067;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x3092;&#x6355;&#x6349;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x30AB;&#x30EB;&#x30E2;&#x30B8;&#x30E5;&#x30EA;&#x30F3;&#x4F9D;&#x5B58;&#x6027;SKCa / IKCa&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x3092;&#x6291;&#x5236;&#x3057;&#x3001;&#x305D;&#x308C;&#x306B;&#x3088;&#x3063;&#x3066;&#x7D30;&#x80DE;&#x8868;&#x9762;&#x4E0A;&#x306B;&#x6A5F;&#x80FD;&#x7684;&#x306A;&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306E;&#x767A;&#x73FE;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x308B;&#x304B;&#x3082;&#x3057;&#x308C;&#x307E;&#x305B;&#x3093;&#x3002; SK3-1C&#x306B;&#x3088;&#x3063;&#x3066;&#x3001;&#x5BB6;&#x65CF;&#x5168;&#x4F53;&#x306E;&#x30C9;&#x30DF;&#x30CA;&#x30F3;&#x30C8;&#x30CD;&#x30AC;&#x30C6;&#x30A3;&#x30D6;&#x6291;&#x5236;&#x306F;&#x3001;&#x7D30;&#x80DE;&#x819C;&#x306E;&#x8208;&#x596E;&#x6027;&#x3092;&#x6EF4;&#x5B9A;&#x3059;&#x308B;&#x305F;&#x3081;&#x306E;&#x5F37;&#x529B;&#x306A;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x3092;&#x63D0;&#x4F9B;&#x3057;&#x3001;&#x5F7C;&#x3089;&#x306E;&#x6A19;&#x7684;&#x30B5;&#x30A4;&#x30EC;&#x30F3;&#x30B7;&#x30F3;&#x30B0;&#x306B;&#x3088;&#x308B;&#x3001;&#x591A;&#x69D8;&#x306A;&#x7D44;&#x7E54;&#x4E2D;&#x306E;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306E;in vivo&#x3067;&#x306E;&#x5F79;&#x5272;&#x3067;&#x6A5F;&#x80FD;&#x3092;&#x5B9A;&#x7FA9;&#x3059;&#x308B;&#x305F;&#x3081;&#x306E;&#x6709;&#x7528;&#x306A;&#x30A2;&#x30D7;&#x30ED;&#x30FC;&#x30C1;&#x3067;&#x3042;&#x308B;&#x3002;

SK3-1C&#x3001;SKCa&#x3068;IKCa&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306E;&#x30C9;&#x30DF;&#x30CA;&#x30F3;&#x30C8;&#x30CD;&#x30AC;&#x30C6;&#x30A3;&#x30D6;&#x6291;&#x5236;

&#xC791;&#xC740; &#xC804;&#xB3C4;&#xB3C4; Ca2 +-&#xD65C;&#xC131;&#xD654; &#xB41C; K + &#xCC44;&#xB110;, &#xC81C;&#xD488; SK1 SK3 &#xC720;&#xC804;&#xC790;&#xC758; &#xC870;&#xC808; &#xB0B4;&#xBD80;&#xC640; &#xC2E0;&#xACBD; &#xC2DC;&#xC2A4;&#xD15C; &#xBC16;&#xC5D0; &#xC11C; &#xB9C9; &#xD765;&#xBD84;. &#xC6B0;&#xB9AC; &#xBCF4;&#xACE0;&#xB294; exon 1A SK3, &#xC0AC;&#xC6A9; &#xD558;&#xB294; &#xB300;&#xC2E0; &#xB300;&#xCCB4; &#xCCAB; &#xBC88;&#xC9F8; &#xC5D1;&#xC190; (exon 1 C)&#xB97C; &#xC774;&#xC6A9; &#xD558; &#xC5EC; sk3&#xC5D0;&#xC11C; &#xB2E4;&#xB974;&#xC9C0;&#xB9CC; SK3 &#xADF8;&#xB807;&#xC9C0; &#xC54A;&#xC73C;&#xBA74; &#xAC19;&#xC2B5;&#xB2C8;&#xB2E4; SK3 variant (SK3-1c)&#xC758; &#xD2B9;&#xC131; &#xBD84;&#xC11D;. &#xC591;&#xC801; RT-PCR &#xC778;&#xAC04;&#xC758; &#xB9BC;&#xD504; &#xC870;&#xC9C1;, &#xACE8;&#xACA9; &#xADFC;&#xC721;, &#xAE30;&#xAD00;, &#xADF8;&#xB9AC;&#xACE0; &#xCE68; &#xC0D8; &#xD558;&#xC9C0;&#xB9CC; &#xC2E0; &#xACBD;&#xACC4; &#xD558;&#xC9C0; C SK3-1 &#xC131;&#xC801; &#xC99D;&#xBA85;&#xC11C;&#xC758; &#xD48D;&#xBD80;&#xD55C; &#xC2DD; &#xAC10;&#xC9C0;. C SK3-1 &#xD3EC;&#xC720;&#xB958; &#xC138;&#xD3EC;&#xC5D0; &#xD63C;&#xC790; &#xD45C;&#xD604; &#xAE30;&#xB2A5; &#xCC44;&#xB110;&#xC744; &#xC0DD;&#xC131; &#xD558;&#xC9C0; &#xC54A;&#xC558;&#xB2E4; &#xD558;&#xC9C0;&#xB9CC; SK1, SK2, SK3, IKCa1 &#xCC44;&#xB110; &#xD558;&#xC9C0;&#xB9CC; k V &#xB610;&#xB294; &#xD558;&#xC9C0; BKCa &#xCC44;&#xB110;&#xC744; &#xC5B5;&#xC81C;. Confocal &#xD604;&#xBBF8;&#xACBD; &#xAC80;&#xC0AC; &#xBC95; &#xACF5;&#xAC1C; C SK3-1 &#xCE68; SK3 &#xB2E8;&#xBC31;&#xC9C8;&#xC744; &#xC555;&#xC218; &#xD588;&#xB2E4;. &#xB54C;&#xBB38;&#xC5D0; calmodulin&#xC758; overexpression SK3 &#xB2E8;&#xBC31;&#xC9C8;&#xACFC; calmodulin&#xC758; &#xC138;&#xD3EC;&#xB0B4; &#xD2B8;&#xB798;&#xD551; SK3 1 C &#xC911;&#xC7AC;&#xB97C; &#xBC18;&#xC804; &#xD558;&#xC9C0; &#xC54A;&#xC558;&#xB2E4; &#xC9C0;&#xBC30; &#xAE08;&#xC9C0; &#xD65C;&#xB3D9; SK3-1 C&#xC758; &#xC77C;&#xBC18;&#xC801;&#xC778; calmodulin &#xC2A4;&#xD380;&#xC9C0; &#xD6A8;&#xACFC;&#xC758; &#xD55C; &#xB418;&#xC9C0; &#xC54A;&#xC558;&#xC2B5;&#xB2C8;&#xB2E4;-Ca2 +-&#xAE30;&#xAC11; &#xBD80; &#xB300; &#xCC44;&#xB110;&#xC758; &#xC885;&#xC18D; &#xBE44;&#xD65C;&#xC131;&#xD654;&#xB294; SK3-1 C overexpression&#xC5D0; &#xC758;&#xD574; &#xC601;&#xD5A5;&#xC744; &#xBC1B;&#xC9C0; &#xC54A;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC0AD;&#xC81C; &#xBD84;&#xC11D; tetramerization &#xCF54;&#xC77C; &#xCF54;&#xC77C; &#xB3C4;&#xBA54;&#xC778; tetramer &#xC548;&#xC815;&#xC131;&#xACFC; &#xB9CE;&#xC740; K + &#xCC44;&#xB110;&#xC758; multimerization&#xC758; &#xC120;&#xD0DD;&#xB3C4; &#xD5A5;&#xC0C1; &#xC2DC;&#xD0A4;&#xAE30; &#xC704;&#xD574; &#xBCF4;&#xACE0; &#xC720;&#xC0AC;&#xD55C; SK3-1 C C &#xB9D0;&#xB2E8;&#xC5D0; &#xC788;&#xB294; &#xC9C0;&#xBC30;&#xC801;&#xC778; &#xC5B5;&#xC81C; &#xC138;&#xADF8;&#xBA3C;&#xD2B8;&#xB97C; &#xC2DD;&#xBCC4; &#xD569;&#xB2C8;&#xB2E4;. SK3-1 C &#xB530;&#xB77C;&#xC11C; &#xD2B8;&#xB798;&#xD551;&#xC774; &#xCC44;&#xB110; &#xB2E8;&#xBC31;&#xC9C8; &#xC18C; &#xB2E8;&#xC704; &#xC0C1;&#xD638; &#xC791;&#xC6A9; &#xC9C0;&#xBC30; &#xAE08;&#xC9C0; &#xC138;&#xADF8;&#xBA3C;&#xD2B8;&#xC5D0; &#xC758;&#xD574; &#xC911;&#xC7AC;&#xB97C; &#xD1B5;&#xD574; &#xCE68;&#xC5D0; &#xC758;&#xD574; calmodulin &#xBB38;&#xC774; SKCa/IKCa &#xCC44;&#xB110;&#xC744; &#xC5B5;&#xC81C; &#xD558; &#xACE0; &#xADF8;&#xB85C; &#xC778;&#xD558;&#xC5EC; &#xC138;&#xD3EC; &#xD45C;&#xBA74;&#xC5D0; &#xAE30;&#xB2A5;&#xC131; &#xCC44;&#xB110; &#xC2DD;&#xC744; &#xC904;&#xC77C; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xAC00;&#xC871; &#xC804;&#xCCB4;&#xC758; &#xC9C0;&#xBC30;&#xC801;&#xC778; &#xBD80;&#xC815;&#xC801;&#xC778; &#xC5B5;&#xC81C; SK3-1 C &#xC801;&#xC815; &#xB9C9; &#xD765;&#xBD84; &#xD558;&#xB294; &#xAC15;&#xB825;&#xD55C; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xC81C;&#xACF5; &#xD569;&#xB2C8;&#xB2E4; &#xADF8;&#xB9AC;&#xACE0; &#xC720;&#xC6A9;&#xD55C; &#xC811;&#xADFC; &#xADF8;&#xB4E4;&#xC758; &#xD0C0;&#xAC9F; &#xC785;&#xC744; &#xC5EC; &#xB2E4;&#xC591; &#xD55C; &#xC870;&#xC9C1;&#xC5D0; &#xC774;&#xB7EC;&#xD55C; &#xCC44;&#xB110;&#xC758; &#xAE30;&#xB2A5;&#xC801; vivo&#xC5D0;&#xC11C; &#xC5ED;&#xD560;&#xC744; &#xC815;&#xC758; &#xD558;&#xB294;.

SK3-1 C, SKCa &#xBC0F; IKCa &#xCC44;&#xB110;&#xC758; &#xC9C0;&#xBC30;&#xC801;&#xC778; &#xBD80;&#xC815;&#xC801;&#xC778; &#xC5B5;&#xC555;.

Peque&#xF1;a conductancia de Ca2 + activados por canales de K +, productos de los genes SK1-SK3, regular la excitabilidad de la membrana, tanto dentro como fuera del sistema nervioso. Se presenta la caracterizaci&#xF3;n de una variante SK3 (SK3-1C) que difiere de SK3 mediante la utilizaci&#xF3;n de un ex&#xF3;n primera alternativa (ex&#xF3;n 1C) en lugar del ex&#xF3;n 1A utilizado por SK3, pero por lo dem&#xE1;s id&#xE9;ntico al SK3. RT-PCR cuantitativa detect&#xF3; abundante expresi&#xF3;n de las transcripciones SK3-1C en humanos los tejidos linfoides, m&#xFA;sculo esquel&#xE9;tico, la tr&#xE1;quea y la gl&#xE1;ndula salivar, pero no el sistema nervioso. SK3-1C no producir canales funcionales cuando se expresan solo en c&#xE9;lulas de mam&#xED;feros, pero suprimidas SK1, SK2, SK3 y canales IKCa1, pero no canales BKCa o KV. La microscop&#xED;a confocal revel&#xF3; que SK3-1C secuestrado SK3 prote&#xED;na intracelular. Dominant actividad inhibidora de SK3-1C no era debido a un efecto calmodulina esponja inespec&#xED;fica ya que la sobreexpresi&#xF3;n de la calmodulina no invirti&#xF3; SK3-1C mediada por atrapamiento intracelular de SK3 prote&#xED;na, y calmodulina Ca2-+-dependiente inactivaci&#xF3;n de los canales de CAV no fue afectada por SK3 sobreexpresi&#xF3;n-1C. Supresi&#xF3;n an&#xE1;lisis identific&#xF3; un segmento dominante inhibitorio en el terminal SK3-1C que se asemeja a C-enrollados en espiral tetramerizaci&#xF3;n dominios reportados para mejorar la estabilidad de tetr&#xE1;mero y la selectividad de multimerizaci&#xF3;n de muchos canales de K +. SK3-1C por lo tanto puede suprimir la calmodulina-dependientes SKCa / IKCa canales atrapando estas prote&#xED;nas intracelularmente canal a trav&#xE9;s de interacciones subunidad mediadas por el segmento dominante-inhibidor y por lo tanto reducir la expresi&#xF3;n funcional del canal en la superficie celular. Esta familia de todo el dominante negativo de la supresi&#xF3;n por SK3-1C proporciona un potente mecanismo para valorar la excitabilidad de la membrana y es un enfoque &#xFA;til para definir el funcional in vivo el papel de estos canales en diversos tejidos por su silenciamiento selectivo.

SK3-1C, un supresor dominante negativo de Canales SKCa y IKCa

&#x5728;&#x6606;&#x866B;&#xFF0C;&#x8D8A;&#x6765;&#x8D8A;&#x591A;&#x7684;&#x8BC1;&#x636E;&#x8868;&#x660E;&#x5C0F;&#x5206;&#x6CCC;&#x7684;&#x7D20;&#x7ED3;&#x5408;&#x86CB;&#x767D; (PBPs) &#x548C;&#x6C14;&#x5473;&#x7ED3;&#x5408;&#x86CB;&#x767D; (OBPs) &#x662F;&#x91CD;&#x8981;&#x7684;&#x6B63;&#x5E38;&#x55C5;&#x89C9;&#x68C0;&#x6D4B;&#x673A;&#x8F7D;&#x4FE1;&#x606F;&#x7D20;&#x53CA;&#x6C14;&#x5473;&#x8FDC;&#x79BB;&#x5176;&#x6765;&#x6E90;&#x3002;&#x76F8;&#x53CD;&#xFF0C;&#x5B83;&#x662F;&#x672A;&#x77E5;&#x662F;&#x5426;&#x80DE;&#x5916;&#x914D;&#x4F53;&#x7ED3;&#x5408;&#x86CB;&#x767D;&#x53C2;&#x4E0E;&#x4F4E;&#x6325;&#x53D1;&#x6027;&#x5316;&#x5B66;&#x7269;&#x8D28;&#xFF0C;&#x5305;&#x62EC;&#x8BB8;&#x591A;&#x4FE1;&#x606F;&#x7D20;&#xFF0C;&#x68C0;&#x6D4B;&#x5230;&#x7684;&#x76F4;&#x63A5;&#x63A5;&#x89E6;&#x4E0E;&#x5316;&#x5B66;&#x611F;&#x53D7;&#x5668;&#x5B98;&#x7684;&#x611F;&#x77E5;&#x3002;CheB42a&#xFF0C;&#x5DF2;&#x77E5;&#x7684; PBPs &#x6216; OBPs&#xFF0C;&#x65E0;&#x5173;&#x7684;&#x5C0F;&#x679C;&#x8747;&#x679C;&#x8747;&#x86CB;&#x767D;&#x8D28;&#x662F;&#x8868;&#x793A;&#xFF0C;&#x5E76;&#x6709;&#x53EF;&#x80FD;&#x4E2D;&#x53EA;&#x6709;&#x4E00;&#x5C0F;&#x90E8;&#x5206;&#x7684;&#x5473;&#x89C9;&#x611F;&#x53D7;&#x5668;&#x5BF9;&#x7537;&#x6027;&#x7684;&#x524D;&#x817F;&#xFF0C;&#x7F51;&#x7AD9;&#x7684;&#x5473;&#x89C9;&#x611F;&#x77E5;&#x7684;&#x8054;&#x7CFB;&#x4EBA;&#x4FE1;&#x606F;&#x7D20;&#x5206;&#x6CCC;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#x6211;&#x4EEC;&#x663E;&#x793A; CheB42a &#x8868;&#x793A;&#x5177;&#x4F53;&#x5728;&#x5468;&#x56F4;&#x8868;&#x793A; Gr68a&#xFF0C;&#x5047;&#x5B9A;&#x5473;&#x89C9;&#x4FE1;&#x606F;&#x7D20;&#x53D7;&#x4F53;&#x523A;&#x6FC0;&#x96C4;&#x6027;&#x6C42;&#x5076;&#x7684;&#x5973;&#x6027;&#x89D2;&#x8D28;&#x5C42;&#x78B3;&#x6C22;&#x5316;&#x5408;&#x7269;&#x7684;&#x5473;&#x89C9;&#x795E;&#x7ECF;&#x5143;&#x7684;&#x9798;&#x7EC6;&#x80DE;&#x3002;&#x4E0D;&#x8FC7;&#xFF0C;&#x5947;&#x602A;&#x7684;&#x662F;&#xFF0C;CheB42a &#x7A81;&#x53D8;&#x7537;&#x6027;&#x8BD5;&#x56FE;&#x65E9;&#x4E9B;&#x65F6;&#x5019;&#x548C;&#x66F4;&#x7ECF;&#x5E38;&#x6BD4;&#x63A7;&#x5236;&#x7537;&#x6027;&#x4E0E;&#x5973;&#x6027;&#x9965;&#x4E0D;&#x62E9;&#x98DF;&#x3002;&#x6B64;&#x5916;&#xFF0C;CheB42a &#x7A81;&#x53D8;&#x7537;&#x6027;&#x8FD8;&#x5C1D;&#x8BD5;&#x66F4;&#x9891;&#x7E41;&#x9965;&#x4E0D;&#x62E9;&#x98DF;&#x5176;&#x4ED6;&#x7537;&#x6027;&#xFF0C;&#x5206;&#x6CCC;&#x9488;&#x5BF9;&#x5973;&#x6027;&#x89D2;&#x8D28;&#x5C42;&#x6CB9;&#x6C14;&#x4FE1;&#x606F;&#x7D20;&#xFF0C;&#x4F46;&#x4E0D;&#x662F;&#x4E0E;&#x5973;&#x6027;&#x7F3A;&#x4E4F;&#x8868;&#x76AE;&#x78B3;&#x6C22;&#x5316;&#x5408;&#x7269;&#x3002;&#x5728;&#x4E00;&#x8D77;&#xFF0C;&#x8FD9;&#x4E9B;&#x6570;&#x636E;&#x8868;&#x660E; CheB42a &#x9700;&#x8981;&#x8C03;&#x8282;&#x7537;&#x6027;&#x6C42;&#x5076;&#x7684;&#x5973;&#x6027;&#x89D2;&#x8D28;&#x5C42;&#x6CB9;&#x6C14;&#x4FE1;&#x606F;&#x7D20;&#x7684;&#x6B63;&#x5E38;&#x5473;&#x89C9;&#x53CD;&#x5E94;&#x3002;

&#x5177;&#x4F53;&#x5230;&#x9065;&#x611F;&#x4FE1;&#x606F;&#x7D20;&#x7684;&#x5473;&#x89C9;&#x6BDB;&#x53D1;&#x7684;&#x679C;&#x8747;&#x86CB;&#x767D;&#x8D28;&#x5EF6;&#x8FDF;&#x7537;&#x6027;&#x7684;&#x4EA4;&#x914D;&#x5C1D;&#x8BD5;&#x3002;

In insects, increasing evidence suggests that small secreted pheromone binding proteins (PBPs) and odorant binding proteins (OBPs) are important for normal olfactory detection of airborne pheromones and odorants far from their source. In contrast, it is unknown whether extracellular ligand binding proteins participate in perception of less volatile chemicals, including many pheromones, that are detected by direct contact with chemosensory organs. CheB42a, a small Drosophila melanogaster protein unrelated to known PBPs or OBPs, is expressed and likely secreted in only a small subset of gustatory sensilla on males' front legs, the site of gustatory perception of contact pheromones. Here we show that CheB42a is expressed specifically in the sheath cells surrounding the taste neurons expressing Gr68a, a putative gustatory pheromone receptor for female cuticular hydrocarbons that stimulate male courtship. Surprisingly, however, CheB42a mutant males attempt to copulate with females earlier and more frequently than control males. Furthermore, CheB42a mutant males also attempt to copulate more frequently with other males that secrete female-specific cuticular hydrocarbon pheromones, but not with females lacking cuticular hydrocarbons. Together, these data indicate that CheB42a is required for a normal gustatory response to female cuticular hydrocarbon pheromones that modulate male courtship.

A Drosophila protein specific to pheromone-sensing gustatory hairs delays males' copulation attempts.

Chez les insectes, plus de preuves sugg&#xE8;re que les petites prot&#xE9;ines s&#xE9;cr&#xE9;t&#xE9;es ph&#xE9;romones contraignantes (PLP) et des prot&#xE9;ines de liaison (odorantes OBPs) sont importantes pour la d&#xE9;tection olfactive normale des ph&#xE9;romones dans l&#x26;#39;air et odorants, loin de leur source. En revanche, on ne sait pas si les prot&#xE9;ines de liaison de ligand extracellulaire participer &#xE0; la perception des produits chimiques moins volatils, y compris les ph&#xE9;romones, les nombreux qui sont d&#xE9;tect&#xE9;s par un contact direct avec les organes chimiosensoriels. CheB42a, une petite prot&#xE9;ine de Drosophila melanogaster rien &#xE0; voir avec PLP connus ou OBPs, est exprim&#xE9; et probablement s&#xE9;cr&#xE9;t&#xE9;e dans seulement un petit sous-ensemble des sensilles gustatives sur les pattes avant des m&#xE2;les, le site de la perception gustative de ph&#xE9;romones de contact. Ici, nous montrons que CheB42a est exprim&#xE9; sp&#xE9;cifiquement dans les cellules de la gaine entourant les neurones exprimant go&#xFB;t Gr68a, un r&#xE9;cepteur de ph&#xE9;romone pr&#xE9;sum&#xE9;e gustative pour les femmes hydrocarbures cuticulaires qui stimulent de s&#xE9;duction des m&#xE2;les. &#xC9;tonnamment, cependant, les m&#xE2;les mutants CheB42a tenter de s&#x26;#39;accoupler avec des femelles plus t&#xF4;t et plus fr&#xE9;quemment que les m&#xE2;les t&#xE9;moins. En outre, les m&#xE2;les mutants CheB42a aussi tenter de s&#x26;#39;accoupler plus souvent avec d&#x26;#39;autres m&#xE2;les qui s&#xE9;cr&#xE8;tent des ph&#xE9;romones sp&#xE9;cifiques aux femmes d&#x26;#39;hydrocarbures cuticulaires, mais pas avec les femmes qui n&#x26;#39;ont pas hydrocarbures cuticulaires. Ensemble, ces donn&#xE9;es indiquent que CheB42a est n&#xE9;cessaire pour une r&#xE9;ponse normale gustative &#xE0; ph&#xE9;romones femelles hydrocarbures cuticulaires qui modulent de s&#xE9;duction des m&#xE2;les.

Une prot&#xE9;ine sp&#xE9;cifique chez la drosophile &#xE0; ph&#xE9;romone-d&#xE9;tection tentatives de copulation gustatives retards Cheveux Hommes des

In Insekten schl&auml;gt die zunehmende Beweise, dass kleine sezernierte Pheromon-bindende Proteine (PBPs) und Odorant-bindende Proteine (OBPs) wichtig f&uuml;r normale olfaktorische Detektion von luftgest&uuml;tzten Pheromone und Geruchsstoffe weit von ihrer Quelle sind. Im Gegensatz dazu ist es unbekannt, ob extrazellul&auml;ren Liganden-bindende Proteine zu beteiligen, in Wahrnehmung der weniger fl&uuml;chtige Chemikalien, darunter viele Pheromone, die durch direkten Kontakt mit chemosensory Organe erkannt werden. CheB42a, eine kleine Drosophila Melanogaster Protein, die nichts mit bekannten PBPs oder OBPs, ist ausgedr&uuml;ckt und wahrscheinlich in nur eine kleine Teilmenge gustatorisches Sensilla auf M&auml;nner Vorderbeine, der Website der gustatorisches Wahrnehmung der Kontakt Pheromone abgesondert. Hier zeigen wir, dass CheB42a ausgedr&uuml;ckt wird, speziell in den Mantel-Zellen, die rund um die Geschmack-Neuronen Ausdr&uuml;cken Gr68a, ein mutma&szlig;liches gustatorisches Pheromon-Rezeptor f&uuml;r weibliche cuticular Kohlenwasserstoffe, die m&auml;nnlichen Brautwerbung zu stimulieren. &Uuml;berraschend, versucht jedoch CheB42a mutant M&auml;nner mit Frauen fr&uuml;her und h&auml;ufiger als Steuerelement M&auml;nnchen kopulieren. Dar&uuml;ber hinaus versucht CheB42a mutant M&auml;nner auch h&auml;ufiger kopulieren mit anderen M&auml;nnchen, die Weibchen-spezifische cuticular Kohlenwasserstoff-Pheromone absondern, aber nicht mit den Weibchen fehlt cuticular Kohlenwasserstoffe. Diese Daten zufolge zusammen, die CheB42a f&uuml;r eine normale gustatorisches Reaktion auf weibliche cuticular Kohlenwasserstoff-Pheromone erforderlich ist, die m&auml;nnlichen Brautwerbung zu modulieren.

Ein Drosophila-Protein, das spezifisch f&uuml;r Pheromon-Sensorik gustatorisches Haare verz&ouml;gert M&auml;nner Kopulation Versuche.

Negli insetti, crescente evidenza suggerisce che piccole feromone secrete binding proteins (PBPs) e odorant binding proteins (OBPs) sono importanti per rilevazione olfattiva normale di feromoni airborne e odorifere lontano dalla loro origine. Al contrario, non &egrave; noto se proteine leganti il ligando extracellulare partecipano nella percezione delle sostanze chimiche meno volatili, tra cui molti feromoni, che vengono rilevati dal contatto diretto con gli organi chemosensory. CheB42a, una piccola proteina di melanogaster della drosofila estraneo conosciuti PBPs o OBPs, &egrave; espresso e probabilmente secreta in solo un piccolo sottoinsieme di sensilli gustativi sulle zampe anteriori dei maschi, il sito di percezione gustativa del contatti feromoni. Qui vi mostriamo che CheB42a &egrave; espresso in particolare nelle cellule guaina che circonda i neuroni di gusto che esprimono un recettore putativo gustativo feromone femminile di idrocarburi cuticolari che stimolano il corteggiamento maschile, Gr68a. Sorprendentemente, per&ograve;, CheB42a mutanti maschi tentano si accoppiano con le femmine prima e pi&ugrave; frequentemente rispetto ai maschi di controllo. Inoltre, i maschi mutanti CheB42a anche tentano si accoppiano pi&ugrave; frequentemente con altri maschi che secernono feromoni idrocarburi cuticolari femmina-specifici, ma non con femmine privo di idrocarburi cuticolari. Insieme, questi dati indicano che CheB42a &egrave; richiesto per una normale risposta gustativa a feromoni femminili idrocarburi cuticolari che modulano il corteggiamento maschile.

Una proteina di drosofila specifica per peli gustativi feromone-sensing ritardi tentativi di accoppiamento dei maschi.

&#x6606;&#x866B;&#x3067;&#x306F;&#x3001;&#x5897;&#x52A0;&#x3059;&#x308B;&#x8A3C;&#x62E0;&#x306F;&#x3001;&#x305D;&#x306E;&#x5C0F;&#x3055;&#x306A;&#x5206;&#x6CCC;&#x30D5;&#x30A7;&#x30ED;&#x30E2;&#x30F3;&#x7D50;&#x5408;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#xFF08;PBPs&#xFF09;&#x3068;&#x5302;&#x3044;&#x7D50;&#x5408;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#xFF08;OBPs&#xFF09;&#x306F;&#x308B;&#x304B;&#x306B;&#x3001;&#x305D;&#x306E;&#x30BD;&#x30FC;&#x30B9;&#x304B;&#x3089;&#x7A7A;&#x4E2D;&#x30D5;&#x200B;&#x200B;&#x30A7;&#x30ED;&#x30E2;&#x30F3;&#x3068;&#x5302;&#x3044;&#x306E;&#x6B63;&#x5E38;&#x306A;&#x55C5;&#x899A;&#x3092;&#x691C;&#x51FA;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x91CD;&#x8981;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3002;&#x5BFE;&#x7167;&#x7684;&#x306B;&#x3001;&#x305D;&#x308C;&#x304C;&#x7D30;&#x80DE;&#x5916;&#x30EA;&#x30AC;&#x30F3;&#x30C9;&#x7D50;&#x5408;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306F;&#x3001;&#x5316;&#x5B66;&#x611F;&#x899A;&#x5668;&#x5B98;&#x3068;&#x306E;&#x76F4;&#x63A5;&#x63A5;&#x89E6;&#x3067;&#x691C;&#x51FA;&#x3055;&#x308C;&#x305F;&#x591A;&#x304F;&#x306E;&#x30D5;&#x30A7;&#x30ED;&#x30E2;&#x30F3;&#x3092;&#x542B;&#x3080;&#x63EE;&#x767A;&#x6027;&#x306E;&#x4F4E;&#x3044;&#x5316;&#x5B66;&#x7269;&#x8CEA;&#x306E;&#x77E5;&#x899A;&#x306B;&#x53C2;&#x52A0;&#x3059;&#x308B;&#x304B;&#x3069;&#x3046;&#x304B;&#x306F;&#x4E0D;&#x660E;&#x3067;&#x3042;&#x308B;&#x3002; CheB42a&#x3001;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;PBPs&#x307E;&#x305F;&#x306F;OBPs&#x3068;&#x306F;&#x7121;&#x95A2;&#x4FC2;&#x306E;&#x5C0F;&#x3055;&#x306A;&#x30AD;&#x30A4;&#x30ED;&#x30B7;&#x30E7;&#x30A6;&#x30B8;&#x30E7;&#x30A6;&#x30D0;&#x30A8;&#x306E;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306F;&#x3001;&#x7537;&#x6027;&#x306E;&#x30D5;&#x30ED;&#x30F3;&#x30C8;&#x306E;&#x8DB3;&#x3001;&#x30B3;&#x30F3;&#x30BF;&#x30AF;&#x30C8;&#x30D5;&#x30A7;&#x30ED;&#x30E2;&#x30F3;&#x306E;&#x5473;&#x899A;&#x77E5;&#x899A;&#x306E;&#x30B5;&#x30A4;&#x30C8;&#x4E0A;&#x306E;&#x5473;&#x899A;&#x611F;&#x899A;&#x5B50;&#x306E;&#x5C0F;&#x3055;&#x306A;&#x30B5;&#x30D6;&#x30BB;&#x30C3;&#x30C8;&#x306E;&#x307F;&#x306B;&#x767A;&#x73FE;&#x3057;&#x3001;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x5206;&#x6CCC;&#x3055;&#x308C;&#x308B;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;CheB42a&#x304C;Gr68a&#x3001;&#x7537;&#x6027;&#x306E;&#x6C42;&#x611B;&#x3092;&#x523A;&#x6FC0;&#x3059;&#x308B;&#x5973;&#x6027;&#x306E;&#x30AF;&#x30C1;&#x30AF;&#x30E9;&#x70AD;&#x5316;&#x6C34;&#x7D20;&#x306E;&#x63A8;&#x5B9A;&#x5473;&#x899A;&#x30D5;&#x30A7;&#x30ED;&#x30E2;&#x30F3;&#x53D7;&#x5BB9;&#x4F53;&#x3092;&#x767A;&#x73FE;&#x3059;&#x308B;&#x5473;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x3092;&#x53D6;&#x308A;&#x5DFB;&#x304F;&#x9798;&#x7D30;&#x80DE;&#x306B;&#x7279;&#x7570;&#x7684;&#x306B;&#x767A;&#x73FE;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x9A5A;&#x304F;&#x3079;&#x304D;&#x3053;&#x3068;&#x306B;CheB42a&#x5909;&#x7570;&#x4F53;&#x306E;&#x96C4;&#x306F;&#x3001;&#x4EE5;&#x524D;&#x3088;&#x308A;&#x983B;&#x7E41;&#x306B;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#x96C4;&#x3088;&#x308A;&#x96CC;&#x3068;&#x4EA4;&#x5C3E;&#x3057;&#x3088;&#x3046;&#x3068;&#x3057;&#x307E;&#x3059;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;CheB42a&#x5909;&#x7570;&#x4F53;&#x306E;&#x96C4;&#x3067;&#x3082;&#x96CC;&#x7279;&#x6709;&#x306E;&#x30AF;&#x30C1;&#x30AF;&#x30E9;&#x70AD;&#x5316;&#x6C34;&#x7D20;&#x30D5;&#x30A7;&#x30ED;&#x30E2;&#x30F3;&#x3092;&#x5206;&#x6CCC;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x4ED6;&#x306E;&#x7537;&#x6027;&#x3068;&#x3088;&#x308A;&#x983B;&#x7E41;&#x306B;&#x4EA4;&#x5C3E;&#x3057;&#x3088;&#x3046;&#x3068;&#x3057;&#x306A;&#x304F;&#x3001;&#x30AF;&#x30C1;&#x30AF;&#x30E9;&#x70AD;&#x5316;&#x6C34;&#x7D20;&#x3092;&#x6B20;&#x304F;&#x96CC;&#x3068;&#x3002;&#x4E00;&#x7DD2;&#x306B;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x306F;&#x3001;CheB42a&#x304C;&#x7537;&#x6027;&#x306E;&#x6C42;&#x611B;&#x3092;&#x8ABF;&#x7BC0;&#x3059;&#x308B;&#x5973;&#x6027;&#x30AF;&#x30C1;&#x30AF;&#x30E9;&#x70AD;&#x5316;&#x6C34;&#x7D20;&#x30D5;&#x30A7;&#x30ED;&#x30E2;&#x30F3;&#x3078;&#x306E;&#x901A;&#x5E38;&#x306E;&#x5473;&#x899A;&#x5FDC;&#x7B54;&#x306B;&#x5FC5;&#x8981;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

&#x30D5;&#x30A7;&#x30ED;&#x30E2;&#x30F3;&#x3092;&#x611F;&#x77E5;&#x3059;&#x308B;&#x5473;&#x899A;&#x6BDB;&#x9045;&#x5EF6;&#x306E;&#x7537;&#x6027; &#x26;quot;&#x4EA4;&#x5C3E;&#x3057;&#x3088;&#x3046;&#x3068;&#x3059;&#x308B;&#x56FA;&#x6709;&#x306E;&#x30B7;&#x30E7;&#x30A6;&#x30B8;&#x30E7;&#x30A6;&#x30D0;&#x30A8;&#x306E;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;

&#xACE4;&#xCDA9;&#xC5D0; &#xC791;&#xC740; &#xBE44; &#xD398;&#xB85C;&#xBAAC; &#xBC14;&#xC778;&#xB529; &#xB2E8;&#xBC31;&#xC9C8; (PBPs) &#xBC0F; odorant &#xBC14;&#xC778;&#xB529; &#xB2E8;&#xBC31;&#xC9C8; (OBPs)&#xB294; &#xACF5; &#xC218; &#xD398;&#xB85C;&#xBAAC; &#xBC0F; &#xADF8;&#xB4E4;&#xC758; &#xC18C;&#xC2A4;&#xAE4C;&#xC9C0; odorants&#xC758; &#xC815;&#xC0C1;&#xC801;&#xC778; &#xD6C4; &#xAC01; &#xAC10;&#xC9C0;&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xC694; &#xD55C; &#xC81C;&#xC548; &#xC99D;&#xAC70;&#xB97C; &#xC99D;&#xAC00;. &#xBC18;&#xBA74;, &#xC138;&#xD3EC; &#xC678; &#xB9AC;&#xAC04;&#xB4DC; &#xBC14;&#xC778;&#xB529; &#xB2E8;&#xBC31;&#xC9C8; &#xC801;&#xAC8C; &#xD718;&#xBC1C;&#xC131; &#xD654;&#xD559; &#xBB3C;&#xC9C8;, chemosensory &#xC7A5;&#xAE30;&#xC640; &#xC9C1;&#xC811; &#xC811;&#xCD09;&#xC5D0; &#xC758;&#xD574; &#xAC80;&#xC0C9; &#xB41C; &#xB9CE;&#xC740; &#xD398;&#xB85C;&#xBAAC; &#xB4F1;&#xC758; &#xC778;&#xC2DD;&#xC5D0; &#xCC38;&#xC5EC; &#xC5EC;&#xBD80;&#xB97C; &#xC54C;&#xB824;&#xC838; &#xD558;&#xC9C0;. CheB42a, &#xC54C;&#xB824;&#xC9C4; PBPs &#xB610;&#xB294; OBPs, &#xAD00;&#xACC4; &#xC5C6;&#xB294; &#xC791;&#xC740; Drosophila melanogaster &#xB2E8;&#xBC31;&#xC9C8; &#xD45C;&#xD604;&#xACFC; &#xAC00;&#xB2A5;&#xC131;&#xC774; &#xC5F0;&#xB77D;&#xCC98; &#xD398;&#xB85C;&#xBAAC;&#xC758; &#xBBF8;&#xAC01;&#xC758; &#xC0AC;&#xC774;&#xD2B8; &#xC791;&#xC740; &#xC218; &#xCEF7;&#xC758; &#xC55E; &#xB2E4;&#xB9AC;&#xC5D0; &#xBBF8;&#xAC01; sensilla&#xC758; &#xD558;&#xC704; &#xC9D1;&#xD569;&#xC5D0; &#xBD84; &#xBE44;. &#xC5EC;&#xAE30; CheB42a Gr68a, &#xC0C1; &#xBBF8;&#xAC01; &#xD398;&#xB85C;&#xBAAC; &#xC218;&#xC6A9; &#xCCB4; &#xC790;&#xADF9; &#xB0A8;&#xC131; &#xAD6C;&#xC560; &#xC5EC;&#xC131; cuticular &#xD0C4; &#xD654; &#xC218;&#xC18C;&#xC5D0; &#xB300; &#xD55C; &#xD45C;&#xD604; &#xB9DB; &#xC2E0;&#xACBD; &#xC138;&#xD3EC;&#xB97C; &#xB458;&#xB7EC;&#xC2F8;&#xACE0; &#xCE7C; &#xC9D1; &#xC140;&#xC5D0;&#xC11C; &#xAD6C;&#xCCB4;&#xC801;&#xC73C;&#xB85C; &#xD45C;&#xD604; &#xD558;&#xB294; &#xAC83;&#xC774; &#xC0B4;&#xD3B4;&#xBCF4;&#xACA0;&#xC2B5;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098; &#xB180;&#xB78D;&#xAC8C;&#xB3C4;,, CheB42a &#xB3CC;&#xC5F0;&#xBCC0;&#xC774; &#xB0A8;&#xC131; &#xC774;&#xC804; &#xBC0F; &#xC81C;&#xC5B4; &#xB0A8;&#xC131; &#xBCF4;&#xB2E4; &#xB354; &#xC790;&#xC8FC; &#xC5EC;&#xC790;&#xC640; &#xC5F0;&#xACB0;&#xD55C; &#xC2DC;&#xB3C4; &#xD569;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C;, CheB42a &#xB3CC;&#xC5F0;&#xBCC0;&#xC774; &#xB0A8;&#xC131;&#xB3C4; &#xC2DC;&#xB3C4; &#xB2E4;&#xB978; &#xB0A8;&#xC131;&#xACFC; &#xC5EC;&#xC131; &#xD2B9;&#xC815; cuticular &#xD0C4;&#xD654;&#xC218;&#xC18C; &#xD398;&#xB85C;&#xBAAC;&#xC744; &#xBD84; &#xBE44; &#xD558;&#xB294; &#xC544;&#xB2C8;&#xC9C0;&#xB9CC; cuticular &#xD0C4; &#xD654; &#xC218;&#xC18C;&#xB97C; &#xBD80;&#xC871; &#xD55C; &#xC5EC;&#xC131;&#xC740; &#xB354; &#xC790;&#xC8FC; &#xC4F0;&#xB2E4;. &#xD568;&#xAED8;, &#xC774;&#xB7EC;&#xD55C; &#xB370;&#xC774;&#xD130; CheB42a &#xB0A8;&#xC131; &#xAD6C;&#xC560; &#xBCC0;&#xC870; &#xC5EC;&#xC131; cuticular &#xD0C4;&#xD654;&#xC218;&#xC18C; &#xD398;&#xB85C;&#xBAAC;&#xC5D0; &#xC815;&#xC0C1; &#xBBF8;&#xAC01; &#xC751;&#xB2F5; &#xD544;&#xC694; &#xD568;&#xC744; &#xB098;&#xD0C0;&#xB0C5;&#xB2C8;&#xB2E4;.

Drosophila &#xB2E8;&#xBC31;&#xC9C8; &#xD398;&#xB85C;&#xBAAC; &#xAC10;&#xC9C0; gustatory &#xBA38;&#xB9AC;&#xCE74;&#xB77D;&#xC5D0; &#xB0A8;&#xC131; &#xACB0;&#xD569; &#xC2DC;&#xB3C4; &#xC9C0;&#xC5F0;.

En los insectos, la evidencia creciente sugiere que las peque&#xF1;as prote&#xED;nas secretadas de feromonas de uni&#xF3;n (PBP) y prote&#xED;nas de uni&#xF3;n a odorantes (OBP) son importantes para la detecci&#xF3;n olfatoria normal de las feromonas en el aire y odorantes lejos de su fuente. Por el contrario, no se sabe si las prote&#xED;nas de uni&#xF3;n al ligando extracelular participar en la percepci&#xF3;n de los productos qu&#xED;micos menos vol&#xE1;tiles, como las feromonas muchos, que son detectados por el contacto directo con los &#xF3;rganos quimiosensoriales. CheB42a, una peque&#xF1;a prote&#xED;na de Drosophila melanogaster no relacionados con PBP conocidos o OBP, se expresa y secreta probable que en s&#xF3;lo un peque&#xF1;o subconjunto de sensilla gustativas en las patas delanteras de los machos, el sitio de la percepci&#xF3;n gustativa de las feromonas de contacto. Aqu&#xED; nos muestran que CheB42a se expresa espec&#xED;ficamente en las c&#xE9;lulas de la vaina que rodea las neuronas que expresan el gusto Gr68a, un receptor putativo de feromonas femeninas gustativa de los hidrocarburos cuticulares que estimulan el cortejo de los machos. Sorprendentemente, sin embargo, CheB42a mutantes machos tratan de aparearse con las hembras antes y con mayor frecuencia que los varones de control. Por otra parte, los hombres CheB42a mutantes tambi&#xE9;n intentan copular con mayor frecuencia con otros machos que secretan las feromonas espec&#xED;ficos de la mujer de hidrocarburos cuticulares, pero no con las mujeres que carecen de hidrocarburos cuticulares. En conjunto, estos datos indican que CheB42a se requiere para una respuesta normal gustativa de las feromonas femeninas de hidrocarburos cuticulares que modulan el cortejo de los machos.

Una prote&#xED;na de Drosophila espec&#xED;fico de detecci&#xF3;n de feromonas-Los intentos gustativas retrasos Pelos de Hombres de la c&#xF3;pula

Autoreactive &#x8BB0;&#x5FC6; T &#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x6709;&#x7275;&#x8FDE;&#x7684;&#x81EA;&#x8EAB;&#x514D;&#x75AB;&#x6027;&#x75BE;&#x75C5;&#x7684;&#x53D1;&#x75C5;&#x673A;&#x5236;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#x6211;&#x4EEC;&#x5C55;&#x793A;&#x4ECE;&#x7C7B;&#x578B; 1 &#x578B;&#x7CD6;&#x5C3F;&#x75C5;&#x3001; &#x7C7B;&#x98CE;&#x6E7F;&#x5173;&#x8282;&#x708E; (RA) &#x60A3;&#x8005;&#x7684;&#x75BE;&#x75C5;&#x5173;&#x8054; autoreactive T &#x7EC6;&#x80DE;&#x6709;&#x9AD8;&#x67B6; Kv1.3 &#x94BE;&#x901A;&#x9053;&#x8868;&#x8FBE;&#x7684;&#x4E3B;&#x8981;&#x662F; CD4 + CCR7 CD45RA &#x6548;&#x5E94;&#x8BB0;&#x5FC6; T &#x7EC6;&#x80DE; &#xFF08;T(EM) &#x5355;&#x5143;&#x683C;&#xFF09;&#x3002;&#x4E0E;&#x6B64;&#x76F8;&#x53CD;&#x7684;&#x662F;&#xFF0C;&#x4E0E;&#x5176;&#x4ED6;&#x6297;&#x539F;&#x7279;&#x70B9;&#x4ECE;&#x8FD9;&#x4E9B;&#x60A3;&#x8005;&#x7684; T &#x7EC6;&#x80DE;&#x6216;&#x4E2A;&#x4EBA;&#x5065;&#x5EB7;&#x548C;&#x75BE;&#x75C5;&#x63A7;&#x5236;&#xFF0C;autoreactive T &#x7EC6;&#x80DE;&#x8868;&#x8FBE;&#x6C34;&#x5E73;&#x4F4E;&#x7684; Kv1.3&#xFF0C;&#x4E3B;&#x8981;&#x662F;&#x5E7C;&#x7A1A;&#x6216;&#x4E2D;&#x592E;&#x5185;&#x5B58; &#xFF08;T(CM)) &#x5355;&#x5143;&#x683C;&#x3002;T(EM) &#x7EC6;&#x80DE;&#x4E2D; Kv1.3 &#x8D29;&#x5356;&#x5230;&#x514D;&#x75AB;&#x7A81;&#x89E6;&#x6297;&#x539F;&#x4ECB;&#x7ECD;&#x5B83;&#x5728; colocalizes &#x671F;&#x95F4;&#x4E0E; Kvbeta2&#x3001; SAP97&#x3001; ZIP&#x3001; p56(lck)&#x3001; CD4&#x3002;&#x867D;&#x7136; Kv1.3 &#x6291;&#x5236;&#x5242; [&#x5B8B;&#x6167;&#x4E54; (L5)-&#x9170;&#x80FA; (SL5) &#x548C; PAP1] &#x4E0D;&#x80FD;&#x9632;&#x6B62;&#x514D;&#x75AB;&#x7A81;&#x89E6;&#x5F62;&#x6210;&#xFF0C;&#x5B83;&#x4EEC;&#x6291;&#x5236; Ca2 +-&#x4FE1;&#x53F7;&#x8F6C;&#x5BFC;&#x3001; &#x7EC6;&#x80DE;&#x56E0;&#x5B50;&#x751F;&#x4EA7;&#x7EC6;&#x80DE;&#x589E;&#x6B96;&#x548C; autoantigen &#x7279;&#x5B9A; T(EM) &#x836F;&#x7406;&#x5B66;&#x76F8;&#x5173;&#x6D53;&#x5EA6;&#x867D;&#x7136;&#x5176;&#x4ED6;&#x7C7B;&#x7684; T &#x7EC6;&#x80DE;&#x3002;Kv1.3 &#x6291;&#x5236;&#x5242;&#x6539;&#x5584;&#x964D;&#x690D;&#x70F7;&#x8BF1;&#x5BFC;&#x5927;&#x9F20;&#x5173;&#x8282;&#x708E;&#x548C;&#x6613;&#x53D1;&#x7CD6;&#x5C3F;&#x75C5; (DP-BB/W&#xFF09; &#x5728;&#x5B9E;&#x9A8C;&#x6027;&#x81EA;&#x8EAB;&#x514D;&#x75AB;&#x6027;&#x7CD6;&#x5C3F;&#x75C5;&#x7684;&#x53D1;&#x751F;&#x7387;&#x964D;&#x4F4E;&#x5927;&#x9F20;&#x3002;&#x5177;&#x6709; Kv1.3 &#x6291;&#x5236;&#x5242;&#x5728;&#x5927;&#x9F20;&#x4E2D;&#x4E00;&#x518D;&#x52A0;&#x836F;&#x540E;&#xFF0C;&#x5E76;&#x672A;&#x53D1;&#x73B0;&#x5168;&#x8EAB;&#x6BD2;&#x6027;&#x3002;&#x56E0;&#x800C; Kv1.3 &#x53D7;&#x4F53;&#x963B;&#x6EDE;&#x5242;&#x6CBB;&#x7597;&#x81EA;&#x8EAB;&#x514D;&#x75AB;&#x6027;&#x75BE;&#x75C5;&#x7684;&#x8FDB;&#x4E00;&#x6B65;&#x53D1;&#x5C55;&#x3002;

Kv1.3 &#x901A;&#x9053;&#x662F; T &#x7EC6;&#x80DE;&#x4ECB;&#x5BFC;&#x7684;&#x81EA;&#x8EAB;&#x514D;&#x75AB;&#x6027;&#x75BE;&#x75C5;&#x7684;&#x6CBB;&#x7597;&#x76EE;&#x6807;&#x3002;

Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression. In contrast, T cells with other antigen specificities from these patients, or autoreactive T cells from healthy individuals and disease controls, express low levels of Kv1.3 and are predominantly naÃ¯ve or central-memory (T(CM)) cells. In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4. Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells. Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats. Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted.

Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases.

Lymphocytes T autor&#xE9;actifs m&#xE9;moire sont impliqu&#xE9;s dans la pathogen&#xE8;se des maladies auto-immunes. Ici, nous d&#xE9;montrons que les cellules associ&#xE9;es &#xE0; la maladie T autor&#xE9;actifs de patients atteints de diab&#xE8;te sucr&#xE9; de type 1 diab&#xE8;te ou l&#x26;#39;arthrite rhumato&#xEF;de (RA) sont principalement CD4 + CCR7-CD45RA-lymphocytes T effecteurs m&#xE9;moire (T (EM) des cellules) dont le taux de Kv1.3 expression des canaux potassiques . En revanche, les cellules T avec d&#x26;#39;autres sp&#xE9;cificit&#xE9;s antig&#xE9;niques de ces patients, ou cellules T autor&#xE9;actives de sujets sains et des contr&#xF4;les de la maladie, expriment des niveaux faibles de Kv1.3 et sont principalement na&#xEF;ve ou central-m&#xE9;moire (T (CM)) des cellules. En T (EM), les cellules Kv1.3 trafics &#xE0; la synapse immunologique au cours de la pr&#xE9;sentation des antig&#xE8;nes o&#xF9; il co-localise avec Kvbeta2, SAP97, ZIP, p56 (LCK) et CD4. Bien que les inhibiteurs Kv1.3 [SHK (L5)-amide (SL5) et PAP1] n&#x26;#39;emp&#xEA;chent pas la formation de la synapse immunologique, ils suppriment Ca2 +-signalisation, la production de cytokines, et la prolif&#xE9;ration des autoantig&#xE8;ne T sp&#xE9;cifiques (EM) des cellules &#xE0; des concentrations pharmacologiquement pertinente tout en en &#xE9;pargnant d&#x26;#39;autres classes de cellules T. Kv1.3 inhibiteurs am&#xE9;liorer pristane arthrite induite chez le rat et de r&#xE9;duire l&#x26;#39;incidence du diab&#xE8;te auto-immune exp&#xE9;rimentale sujet au diab&#xE8;te (DP-BB / W) chez le rat. L&#x26;#39;administration r&#xE9;p&#xE9;t&#xE9;e avec Kv1.3 inhibiteurs chez le rat n&#x26;#39;a pas r&#xE9;v&#xE9;l&#xE9; une toxicit&#xE9; syst&#xE9;mique. Poursuite du d&#xE9;veloppement du Kv1.3 bloquants pour le traitement des maladies auto-immunes est justifi&#xE9;e.

ArticleTotal : 66	Year
Publication title Cited by 19	2007
Publication title Cited by 1	2007
Publication title	2007
Publication title Cited by 38	2007
Publication title	2012

Article	Year
SK3-1C, a dominant-negative suppressor of SKCa and IKCa channels. The Journal of biological chemistry\| PubMed ID: 14638680	2004
A Drosophila protein specific to pheromone-sensing gustatory hairs delays males' copulation attempts. Current biology : CB\| PubMed ID: 16753571	2006
Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 17088564	2006
Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. Current medicinal chemistry\| PubMed ID: 17584055	2007

Aaron Kolski-Andreaco

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