Name: membrane lipid flipping and transport
Uploaded: 2023-04-30T10:41:36.000Z
Duration: 1 min 19 s
Channel: JoVE

K12 Standards

Alabama Course of Study Science

9-12

Biology

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

9-12.B.1.4.a

membrane-asymmetry-regulating-transporters

Membrane Asymmetry Regulating Transporters

膜の非対称性は、二重層を介してリン脂質を転位させる3種類のトランスポーターによって制御されています。
Flippaseは、ホスファチジルセリンとホスファチジルエタノールアミンを外層から内層に移動するATP依存性脂質輸入体です。
フロッパーゼは、脂質を内層から外層に輸送するATP依存性の非特異的脂質エクスポーターです。フリップパーゼとフロッパーゼはどちらも、膜の非対称性を生成する上で重要な役割を果たします。
スクランブラーゼはATPに依存しないトランスポーターであり、両方の層での脂質のランダムな移動を可能にし、それによって膜の非対称性を低減します。赤血球では、スクランブラーゼは細胞内カルシウムの正常な生理学的レベルでは不活性であり、カルシウムイオン濃度が増加すると活性化されます。 
スクランブラーゼの活性化は、ホスファチジルセリンを内膜層から外膜層に移すことができます。ホスファチジルセリンの外部への曝露は、赤血球を紅葉症として知られる自殺死のマークし、マクロファージによるそれらの除去を引き起こします。

トランスポーターを調節する膜の非対称性

フリッパーゼ、フロッパーゼ、スクランブラーゼなどの酵素は、膜内でリン脂質をある層から別の層に移動させ、それによって膜の非対称性に影響を与えます。

フリッパーズ

真核生物のフリッパーゼは、IV 型 P 型 ATPase または P4-ATPase で、膜を通過できるようにしますイオンおよび分子の ATP 媒介輸送に関与する膜結合ポンプである P 型 ATPase ファミリータンパク質に属します。 フリッパーゼは、特定のリン脂質を膜の外側から内側へ反転させます。 すべての P4-ATPase は、10 個の膜貫通αヘリックスを含む 1 つの膜貫通ドメインと 3 つの細胞質ドメインを持っています。 3 つの細胞質ドメインには、ヌクレオチド結合ドメイン、リン酸化ドメイン、および脱リン酸化ステップに関与するアクチュエーター ドメインが含まれます。

フロッパーゼ

フロッパーゼは、さまざまなリン脂質を膜の内側から外側のリーフレットに輸送する ATP 結合カセットまたは ABC トランスポーターファミリータンパク質に属します。 このファミリーの必須タンパク質には、ABCA1、ABCA4、ABCB1、ABCB4 などがあります。 ABCA1 フロッパーゼはコレステロールを膜の内側から外側へ移動させることができ、その変異によりタンジェ病が引き起こされる可能性があります。

スクランブラーゼ

スクランブラーゼは、フリッパーゼやフロッパーゼとは異なり、ATP 加水分解からのエネルギーを使用せずに膜内のリン脂質の双方向移動を行うことができます。 細胞には、膜貫通タンパク質 16F (TMEM16F) と XK 関連タンパク質 8 (Xkr8) の 2 種類のスクランブラーゼが存在します。 TMEM16Fスクランブラーゼは血小板膜内に位置しており、活性化には高濃度のカルシウムイオンが必要です。 対照的に、カスパーゼはアポトーシス中に細胞膜内の Xkr8 を活性化します。 スクランブラーゼの発現異常により、スコット症候群と呼ばれる出血性疾患が引き起こされます。

フリップパーゼ、フロッパーゼ、スクランブラーゼなどの酵素は、リン脂質を膜内のある層から別の層に輸送するため、膜の非対称性に影響を及ぼします。
...

Education

JoVE Core

Cell Biology

細胞生物学

Unit 1

ユニット1

Membrane Structure and Components

膜構造とその構成成分

KEY TERMS AND CONCEPTS

主要用語と概念

membrane lipid flipping and transport

Membrane lipid flipping and transport help cells keep an uneven, or asymmetric, distribution of phospholipids across the membrane. This balance is controlled by flippase, floppase, and scramblase enzymes, which move lipids between the two membrane leaflets.

Flippases move specific phospholipids from the outer leaflet to the inner leaflet. In eukaryotes, these enzymes are type-IV P-type ATPases, also called P4-ATPases. They are membrane pumps that use ATP and contain one transmembrane domain with ten transmembrane alpha-helices and three cytoplasmic domains: a nucleotide-binding domain, a phosphorylation domain, and an actuator domain that helps with dephosphorylation.

Floppases move phospholipids in the opposite direction, from the inner leaflet to the outer leaflet. They belong to the ATP-binding cassette, or ABC-transporter, family. Important members include ABCA1, ABCA4, ABCB1, and ABCB4. ABCA1 can move cholesterol to the outer leaflet, and mutation of ABCA1 can lead to Tangier disease.

Scramblases work differently from flippases and floppases. They move phospholipids in both directions and do not use ATP hydrolysis for energy. Two scramblases found in cells are TMEM16F and Xkr8. TMEM16F is found in platelet membranes and needs a high calcium ion level for activation, while caspase activates Xkr8 during apoptosis. When scramblase expression is defective, it can cause the bleeding disorder Scott syndrome.

Membrane Lipid Flipping and Transport

what are membranes?

Membrane Receptors and Cell Signals

The plasma membrane sets the outer boundary of a cell and helps control how the cell interacts with its environment. It lets some substances enter, keeps others out, and releases some materials in controlled amounts. The membrane also needs to stay flexible so cells such as red and white blood cells can change shape as they move through narrow capillaries. The membrane surface also carries markers that help cells recognize one another. This recognition is important during early development,...

membrane fluidity

How Cell Membranes Stay Flexible

Cell membranes stay flexible because of the fluid mosaic model. The plasma membrane is a mosaic of phospholipids, cholesterol, proteins, and carbohydrates. These parts are separate but loosely attached, so the membrane keeps a fluid character. The membrane is still fairly rigid, but it can flow and self-seal after a very fine needle passes through it. Phospholipid tails also affect membrane fluidity. Saturated fatty acids in phospholipids have straight tails because they are packed with...

fluid mosaic model

Fluid Mosaic Model of the Membrane

The fluid mosaic model explains the structure and function of the plasma membrane. Scientists first identified the plasma membrane in the 1890s, and by 1915 they had identified its main chemical parts: lipids and proteins. Early electron micrographs showed a railroad track pattern, which helped lead to the first widely accepted membrane model in 1935.

membrane lipids

Membrane Lipids in Cells and Tissues

Membrane lipids give biological membranes their structure and help set their properties. In mammalian cells, lipids make up about 50% of the membrane on average. The amount can be much lower in the inner mitochondrial membrane or much higher in the myelin sheath around nerve cells. Several phospholipids are common in mammalian membranes. These include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin. At physiological pH, phosphatidylserine carries a negative...

asymmetric lipid bilayer

Membrane Lipid Unevenness

Biological membranes have an uneven mix of lipids between the inner and outer layers. This membrane asymmetry gives each side a different chemical makeup and supports different cell functions. Evidence for this uneven layout came from treating an erythrocyte membrane with phospholipase. Phospholipase is an enzyme that breaks lipids into fatty acids and hydrophilic groups. It acted only on the outer layer, while the inner layer stayed intact. The treatment degraded about 80% of total membrane...

membrane asymmetry regulating transporters

Membrane lipid flipping and transport help cells keep an uneven, or asymmetric, distribution of phospholipids across the membrane. This balance is controlled by flippase, floppase, and scramblase enzymes, which move lipids between the two membrane leaflets. Flippases move specific phospholipids from the outer leaflet to the inner leaflet. In eukaryotes, these enzymes are type-IV P-type ATPases, also called P4-ATPases. They are membrane pumps that use ATP and contain one transmembrane domain...

membrane carbohydrates

Membrane Sugars and Cell Identity

Membrane carbohydrates help give cells their surface identity and support plasma membrane function. The plasma membrane is a dynamic barrier made of lipids, proteins, and carbohydrates. These sugar chains have unique structural and chemical traits that help the membrane work properly for cell growth and survival. Membrane carbohydrates do not have a hydrophobic region, so they are found only on the outer surface of the cell. Sugar addition, or glycosylation, of proteins occurs in the lumens of...

membrane proteins

Facilitated Transport Across Cell Membranes

Facilitated transport uses membrane proteins to help materials cross the plasma membrane. These integral transmembrane proteins act as channels or carriers. They move selected substances through the membrane more easily than the lipid layer alone would allow. Channel proteins provide a hydrophilic, or water-friendly, path through the membrane. Their core forms a hydrated opening that lets solutes pass between the inside and outside fluids of the cell. This helps polar compounds avoid the...

lipids as anchors

Lipid Anchors in Membrane Proteins

Lipid anchors help attach proteins to the plasma membrane. In eukaryotic cells, the main lipid anchors are prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol, or GPI, groups. Prenyl and fatty acyl groups anchor proteins on the cytosolic side of the membrane. GPI anchors proteins on the extracellular side. Prenylated proteins often have a CaaX motif at the carboxy terminus. In this sequence, C means cysteine, a means any aliphatic amino acid, and X means any other amino acid...

single-pass transmembrane proteins

How Membrane Proteins Span Cell Membranes

Membrane proteins help cells communicate, send signals, stick to other cells, and move molecules across the membrane. Integral membrane proteins are tightly linked to the cell membrane and carry out these jobs. Some integral membrane proteins sit only in one membrane layer. Fatty acid amide hydrolase is one example, and it is found on the cytoplasmic side of the membrane monolayer. Other integral membrane proteins are transmembrane proteins, which span across the membrane. These proteins have...

multi-pass transmembrane proteins and &#946;-barrels

multi-pass-transmembrane-proteins-and-barrels

Membrane-Spanning Helices and β-Barrels

Membrane-spanning proteins can cross the cell membrane more than once. Their transmembrane chain usually folds into either an alpha-helix or a beta-strand. Alpha-helix multi-pass proteins are common, while beta-strand proteins are found mainly in gram-negative bacteria, mitochondria, and chloroplasts. Some multi-pass alpha-helix proteins are G-protein-linked receptors, or GPCRs, and bacteriorhodopsin. GPCRs have seven transmembrane alpha-helices. Each receptor also has its own extracellular...

detergent purification of membrane proteins

detergent-purification-of-membrane-proteins

How Detergents Solubilize Membrane Proteins

Detergents help solubilize membrane proteins so they can be purified from the lipid bilayer. Their hydrophobic region can replace membrane phospholipids and keep integral membrane proteins in solution. A detergent works well only when its monomers reach the critical micelle concentration, or CMC. At that point, the molecules assemble into micelles, which are small clusters of detergent. Above the CMC, free detergent monomers stay in equilibrium with the micelles. The CMC varies with the...

protein diffusion in the membrane

How Membrane Proteins Move Side to Side

Membrane proteins can move across the cell surface by lateral diffusion, and they can also rotate in place. Scientists confirmed lateral movement with a cell fusion experiment. Mouse and human cells were fused to make hybrid cells. The membrane proteins on the two cells were tagged with red and green fluorescent markers. At first, each color stayed on its own side of the fused cell. After 40 minutes, the colors mixed across the whole cell surface, showing that the proteins had moved laterally. <br...

membrane domains

Lipid Rafts and Sperm Membrane Regions

Membrane domains organize specific lipids and proteins in defined parts of a cell membrane. This arrangement supports cell signaling, adhesion, and other important cellular processes. These domains can vary in size, composition, function, and how long they last. Some membrane domains are built from proteins. The membrane can contain distinct protein groups that carry out a cell’s specific functions. A clear example is the plasma membrane of a human sperm cell, which has different proteins in...

mechanisms of membrane domain formation

How Cell Membranes Form Domains

Cell membranes form domains when lipids and proteins gather into distinct regions. These regions, or membrane domains, are shaped by different physical properties that help some molecules stay together while others move apart. Some domains form through protein-protein interactions. Others depend on specific lipids, such as sphingolipids and sterols. Large proteins, including bacteriorhodopsin, can also cluster and create visible membrane domains. Membrane proteins can be held in place by...

mechanisms of membrane-bending

How Proteins Shape Cell Membranes

Cell membranes can bend into many shapes because they are flexible and made of a fluid mosaic. That bending can be temporary, as in vesicles, or long-lasting, as in microvilli. Cells control the size, place, and time of membrane curvature. Membrane bending can start inside the membrane itself or from proteins attaching to it. Changes in lipid makeup can create curvature, and proteins can help by making the membrane asymmetric or by clustering certain lipids. The shape of integral proteins also...

key terms and concepts

Learn how flippases, floppases, and scramblases move phospholipids across membranes and help maintain membrane asymmetry in cells.

Membrane Lipid Flipping and Transport | JoVE K12

cell biology

JoVE Core 細胞生物学は、複雑な細胞プロセスを、わかりやすく包括的なアニメーション ビデオ レッスンで説明します。このコレクションは、細胞小器官や膜、細胞輸送、細胞のエネルギー学など、細胞の必須コンポーネントと機能に焦点を当てています。これは、実際の研究実験における細胞生物学の応用を実証する科学者による実際のビデオによって補足されています。

What are Cells?

Cells are the smallest and basic units of life, whether it is a single cell that forms the entire organism, e.g., in a bacterium or trillions of them, ...

Cell Size

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Eukaryotic Compartmentalization

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Prokaryotic Cells

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Cytoplasm

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The Nucleus

The nucleus is a membrane-bound organelle that acts as a control center in a eukaryotic cell. It contains chromosomal DNA, which controls gene expression ...

Endoplasmic Reticulum

Endoplasmic ReticulumThe endoplasmic reticulum (ER) is an extensive network of membranous sacs and tubules in eukaryotic cells, continuous with the outer ...

Ribosomes

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Golgi Apparatus

As they leave the Endoplasmic Reticulum (ER), properly folded and assembled proteins are selectively packaged into vesicles. These vesicles are ...

Lysosomes

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Peroxisomes

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Introduction to the Cytoskeleton

Overview of the Cytoskeleton
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Introduction to Actin

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Overview of Myosin Structure and Function

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Microtubules

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The Structure of Intermediate Filaments

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Types of Intermediate Filaments

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Gap Junctions

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The Extracellular Matrix

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Tissues

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Plant Cell Wall

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Plasmodesmata

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pH Regulation in Cells

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Chemistry of the Cell

Introduction to Cellular Respiration

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ATP Energy Storage and Release

ATP and Macromolecule Synthesis

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1. Engage in evidence-based argument to relate a cell's function to the structure, function, and diversity of its components. Examples: Muscle cells have a large number of mitochondria, which create energy for contraction in the form of ATP. Some plant cells have a large vacuole which is used for storage and transport of excess nutrients in changing environments.

9-12.B.1.1

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised&#160; of nucleotides and proteins are ...

RNA Structure

The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form ...

Types of RNA

Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse ...

Transcription

Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. ...

Bacterial RNA Polymerase

Eukaryotic RNA Polymerases

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of ...

RNA Polymerase II Accessory Proteins

Transcription Elongation Factors

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Pre-mRNA Processing: Modification of pre-mRNA Ends

In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or ...

Pre-mRNA Processing: RNA Splicing

Chromatin Structure and RNA Splicing

Alternative RNA Splicing

Nuclear Export of mRNA

Transfer RNA Synthesis

Ribosomal RNA Synthesis

The Nucleolus

Additional Subnuclear Structures

Translation

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes ...

tRNA Activation

Initiation of Translation

Termination of Translation

Improving Translational Accuracy

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Prokaryotic Transcriptional Activators and Repressors

Nonsense-mediated mRNA Decay

The Eukaryotic Promoter Region

Molecular Chaperones and Protein Folding

Co-activators and Co-repressors

The Proteasome

Master Transcription Regulators

Regulated Protein Degradation

Regulated mRNA Transport

Proteins: From Genes to Degradation

mRNA Stability and Gene Expression

Cell Specific Gene Expression

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between ...

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Regulation of Expression Occurs at Multiple Steps

Small interfering RNAs (siRNA)

Cis-regulatory Sequences

lncRNA - Long Non-coding RNAs

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Cooperative Binding of Transcription Regulators

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. ...

2. Obtain and evaluate information to explain the role of DNA and RNA in transcription and translation leading to protein synthesis and cellular function.

9-12.B.1.2

Nucleic Acids and Nucleotides

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Nucleic Acid Structure

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Genomic DNA in Prokaryotes

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Genomic DNA in Eukaryotes

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The DNA Helix

Overview

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a. Use a model to describe the structure and sequence of DNA, including nucleotide structure, base pairing, and the structure of the helix.

9-12.B.1.2.a

Membrane Lipid Flipping and Transport

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