Name: tight junction proteins and cell barriers
Uploaded: 2023-04-30T11:55:38.000Z
Duration: 1 min 29 s
Channel: JoVE

W narządach takich jak nerki i jelita komórki nabłonkowe są uszczelnione ścisłymi połączeniami, aby zapobiec przepływowi makrocząsteczek, jonów i małych substancji rozpuszczonych przez przestrzeń parakomórkową.
Ścisłe połączenia obejmują głównie białka transbłonowe klaudyny i okludyny, z których każde ma cztery alfa-helisy obejmujące błonę.
Rzędy klaudyn i okludyn polimeryzują na błonie, tworząc sieć pasm uszczelniających.
Pasma te przyczepiają się do podobnych pasm białek na sąsiedniej komórce za pomocą pętli zewnątrzkomórkowych, utrzymując w ten sposób obie błony razem.
Po stronie cytoplazmatycznej C-końcowe ogony tych białek łączą się z domenami PDZ dużych białek rusztowania zwanych zonula occludens lub ZO.
Białka ZO mają wiele domen wiążących białka i mogą w ten sposób wiązać klaudyny, okludyny, aktynę i inne białka ZO, tworząc siatkę, która organizuje i stabilizuje te nici uszczelniające.
Oprócz uszczelniania przestrzeni parakomórkowej, ścisłe połączenia zapobiegają również bocznemu ruchowi białek, takich jak transportery glukozy, wzdłuż błony. Pomaga to zlokalizować te białka na wierzchołkowej powierzchni nabłonka jelitowego w celu wchłonięcia glukozy.

<ol>
	<li>Sawada, Norimasa. "Choroby człowieka związane ze ścisłymi połączeniami." Patologia międzynarodowa 63.1 (2013): 1-12. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168075/">Link</a></li>
	<li>Anderson, James M. i Christina M. Van Itallie. "Fizjologia i funkcja ścisłego połączenia." Perspektywy Cold Spring Harbor w biologii 1.2 (2009): a002584. <a href="https://cshperspectives.cshlp.org/content/1/2/a002584.full">Link</a></li>
	<li>Mariano, Cibelle, et al. "Spojrzenie na tricelulinę i jej rolę w tworzeniu i utrzymaniu połączeń ścisłych". Europejski dziennik biologii komórki 90.10 (2011): 787-796. <a href=" https://d1wqtxts1xzle7.cloudfront.net/52322075/A_look_at_tricellulin_and_its_role_in_ti20170327-17112-1qhpwe8-libre.pdf?1490608194=&response-content-disposition=inline%3B+filename%3DA_look_at_tricellulin_and_its_role_in_ti.pdf&Expires=1654205963&Signature=IelR0FUZCC6ZcqAcJvs1JTGe6liRDBX6aqaYzcw4sMZ2yqyhu5BuZ9DDbujaDRUN9SwX20yuCRLRyzxl6MWAa4QfY2cZ1wtZb4qfoi5otW~z0rhB3ba231uB1~pdP0rZpdHB4~snYhLr-~nZRsoaUqTFJmJaJXpxtHnoBGC4HFP29Q8D3q0rNHNDJGq9Qx9SfcLWmDISH7n8IfsUozT6rdpn421eOVufn5lNVunpqMX6iiRAT4D7p8bJEPpfd2~3cygJP7Ltc32RiIm2RHGvp9CRUoXs015y2aR4A7--dka7UzL97Aa~DDZ8ES90wX9D58qA~jX24DnmzNeNwlAayg__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA">Link</a></li>
</ol>

połączenia ścisłe

Tight Junctions

Połączenia ścisłe to molekularne uszczelnienia między komórkami, które zapobiegają wyciekaniu płynów, jonów i innych małych substancji rozpuszczonych przez wnęki i przedziały organizmów wielokomórkowych. Składają się głównie z białek transbłonowych klaudyny i okludyny oraz innych białek, takich jak tricelulina i JAM (cząsteczka adhezji złączowej). Wszystkie te białka są 4-przebiegowymi białkami transbłonowymi, z wyjątkiem JAM, który jest jednoprzebiegowym białkiem transbłonowym należącym do nadrodziny immunoglobulin. Domeny zewnątrzkomórkowe tych białek ścisłych połączeń oddziałują z domenami na sąsiedniej błonie komórkowej, łącząc w ten sposób i uszczelniając dwie sąsiadujące komórki. 

 Selektywna przepuszczalność połączeń ścisłych 

 Istnieje wiele izoform przezbłonowej klaudyny, z czego aż 24 różne typy ulegają ekspresji u ludzi. Różnorodność białka klaudyny nadaje selektywną przepuszczalność różnym ścisłym połączeniom. Na przykład klaudyna-16, wyrażana w nabłonku nerek, zwiększa przepuszczalność jonów magnezu, umożliwiając w ten sposób ich ponowne wychwytywanie z krwi podczas filtracji. Natomiast klaudyna-5 wyrażana w komórkach śródbłonka naczyń włosowatych mózgu selektywnie zmniejsza przepuszczalność jonów przez barierę krew-mózg. 

 Połączenia trójkomórkowe 

 Oprócz uszczelniania szczelin między dwiema komórkami, szczelne połączenia uszczelniają również szczeliny powstałe na styku trzech komórek - połączenie trójkomórkowe. Strukturę połączeń trójkomórkowych po raz pierwszy zaobserwowano w latach 70. XX wieku za pomocą mikroskopii elektronowej z zamrożeniem i pękaniem. W tych połączeniach pasma uszczelniające są zorientowane prostopadle do pasm dwukomórkowych połączeń ścisłych. Trójkomórkowy punkt kontaktowy tworzy w ten sposób wąską pionową rurkę o średnicy około 10 nm, która kontroluje parakomórkowy ruch cząsteczek. 

 Tricelulina była pierwszym zidentyfikowanym białkiem skupiającym się w tych połączeniach trójkomórkowych. Ma homologię sekwencji z białkami okludyny i u ludzi wykazuje cztery izoformy. Co ciekawe, wykazano, że mutacje w genie triceluliny, TRIC, powodują upośledzenie słuchu, co wskazuje na jego znaczenie w utrzymywaniu szczelnych połączeń, takich jak te wymagane w narządzie Cortiego – strukturze ucha wewnętrznego.

Połączenia ścisłe

Ścisłe połączenia to molekularne uszczelnienia między komórkami, które zapobiegają wyciekom płynów, jonów i innych małych substancji rozpuszczonych przez wnęki i przedziały w ...

Education

JoVE Core

Cell Biology

Biologia komórki

Unit 1

Jednostka 1

Cell-Cell Interactions

Interakcje międzykomórkowe

KEY TERMS AND CONCEPTS

Kluczowe terminy i pojęcia

tight junction proteins and cell barriers

Tight junction proteins form seals between neighboring cells. These molecular barriers help stop fluids, ions, and other small solutes from leaking across body cavities and tissue compartments in multicellular organisms. They are an important part of cell barriers in places where controlled movement matters.

The main tight junction proteins are claudin and occludin. Other proteins include tricellulin and JAM, which stands for junctional adhesion molecule. Most of these proteins are 4-pass transmembrane proteins, meaning they cross the cell membrane four times. JAM is different because it is a single-pass transmembrane protein in the immunoglobulin superfamily. The extracellular parts of these proteins interact with matching parts on the nearby cell membrane. This brings two adjacent cells together and helps seal them.

Claudin proteins are especially important because there are many isoforms, or forms, of claudin. Humans express up to 24 different types. This diversity gives tight junctions selective permeability, which means some substances pass more easily than others. For example, claudin-16 in kidney epithelium increases permeability to magnesium ions. This helps magnesium move back into the body during filtration. In contrast, claudin-5 in endothelial cells of brain capillaries lowers ion permeability across the blood-brain barrier.

Tight junctions also seal tricellular junctions, which are the gaps where three cells meet. These junctions were first seen in the 1970s with freeze-fracture electron microscopy. At these contact points, the sealing strands run perpendicular to the strands in bicellular tight junctions. The center of the tricellular contact forms a narrow vertical tube about 10 nm wide. This structure helps control paracellular movement, which is movement between cells.

Tricellulin is the first protein known to concentrate at tricellular junctions. It is related in sequence to occludin and has four isoforms in humans. Mutations in the tricellulin gene, TRIC, can cause hearing impairment. This shows how important tight seals are in the organ of Corti, a structure in the inner ear.

Tight Junction Proteins and Cell Barriers

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cell adhesion molecules - types and functions

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Cell Adhesion Molecules in Tissues

Cell adhesion molecules help cells stick together and work as part of a tissue. They give multicellular organisms physical strength and also help cells send signals across the plasma membrane. These proteins are important for coordinated activity in tissues and organ systems. CAMs are grouped into four main families: integrins, cadherins, selectins, and immunoglobulin-like CAMs, or IgCAMs. Each family supports cell interactions in a different way. Some CAMs help cells attach firmly, while...

structure of cadherins

Cadherins in Cell Junctions and Disease

Cadherins are cell adhesion proteins that help cells stick together and build tissues. Their name comes from their calcium-dependent binding. Early examples were named E-cadherin, P-cadherin, and N-cadherin after the epithelial, placental, and neuronal cells where they were first found. Classical cadherins share similar sequences and structures. Other cadherins, including those involved in cell signaling, are grouped as non-classical cadherins. This diversity comes from multiple cadherin genes...

cadherins in tissue organization

Cadherins Guide Cell Sorting in Tissues

Cadherins help cells sort into the right tissues during development. They are a large superfamily of cell adhesion molecules, with more than 180 variants. Different tissues express specific cadherin combinations, which helps cells recognize and stick to the right neighbors. Cadherins usually bind to the same or a closely related cadherin on another cell. This is called homophilic binding. Because of this matching behavior, cells of the same type tend to group together and form clusters that...

catenins

Catenins in Cell Junctions and Signaling

Catenins help cells stay connected and also support signaling inside the body. These proteins act as linker proteins in cell junction complexes because they have multiple binding domains and flexible structures. Most catenins contain a protein sequence called the armadillo repeat, so they are also known as armadillo proteins. Alpha-catenin is the main exception. Catenins bind to cell adhesion molecules such as cadherins. They then connect cadherins to cytoskeletal proteins, and the exact link...

selectins

Selectins in Immune Cell Capture

Selectins help cells make short, temporary contacts during immune responses. They are cell adhesion molecules that bind carbohydrate ligands on other cells. These rod-like proteins have a long outside region and end in a lectin domain, which binds carbohydrates only when calcium ions are present. Three main selectins are known: L-selectin, P-selectin, and E-selectin. Their names reflect where they are found and how long they are. This tissue specificity helps explain why selectins act in...

immunoglobulin-like cell adhesion molecules

immunoglobulin-like-cell-adhesion-molecules

Ig-CAMs in Neural Growth and Disease

Ig-CAMs, or immunoglobulin-like cell adhesion molecules, are cell surface glycoproteins in the immunoglobulin superfamily. They contain immunoglobulin domains, and some also have fibronectin type III domains. Their Ig domains can be glycosylated to different degrees. These molecules can bind to the same kind of Ig-CAM or to other ligands, such as integrins. Most Ig-CAMs help cells stick together only for a short time. The nectin class is different because it helps form stable junctions,...

overview of cell-cell junctions

Cell Junctions in Tissues

Cell junctions help hold tissues together and let neighboring cells communicate. In multicellular organisms, the three-dimensional shape of tissues depends on interactions between cells and the extracellular matrix. Cell-cell junctions are specialized structures made of multi-protein complexes on one cell that connect with similar complexes on another cell. These junctions are grouped into three main types based on function: occluding, anchoring, and gap junctions. Tight junctions, also called...

adherens junctions

Cell Adhesion in Tissues and Infection

Adherens junctions are strong cell-to-cell anchors that help tissues stay connected. These anchoring junctions work with desmosomes, another type of junction that holds adjacent cells together. In many epithelial and endothelial tissues, adherens junctions form a continuous adhesion belt. In heart muscle, they often appear as clusters that help cells work together for coordinated contraction. Adherens junctions are also dynamic, especially in the cells that line blood vessels. These...

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How Adherens Junctions Sense Force

Adherens junctions help cells stay attached while they respond to mechanical force. These multi-protein complexes can adapt to tensile force and shear stress. When the force changes, mechanosensory proteins in the junction can change shape. This process is called mechanotransduction. Alpha-catenin is one of the main force-sensing proteins in adherens junctions. It is an allosteric protein, which means its shape affects how it works. Alpha-catenin has three VH, or vinculin homology, domains...

desmosomes

Desmosomes and Cell Anchoring

Desmosomes are cell junctions that anchor cells together. They are button-like structures that create an interlinked network of intermediate filaments across cells. This strong link helps tissues resist mechanical stress and maintain tissue integrity. Desmosomes are built from multiple proteins. Their core includes desmosomal cadherins, which are adhesion proteins that bind to cadherins on neighboring cells. The two desmosomal cadherins are desmogleins and desmocollins. These transmembrane...

tight junctions

Tight junction proteins form seals between neighboring cells. These molecular barriers help stop fluids, ions, and other small solutes from leaking across body cavities and tissue compartments in multicellular organisms. They are an important part of cell barriers in places where controlled movement matters. The main tight junction proteins are claudin and occludin. Other proteins include tricellulin and JAM, which stands for junctional adhesion molecule. Most of these proteins are 4-pass...

gap junctions

Cell Communication Through Gap Junctions

Gap junctions let adjacent animal cells share small molecules, ions, and secondary messengers. These communication channels connect the cytoplasm of neighboring cells. They are built from many molecular channels, often from a few hundred to thousands in one junction. Each channel is made of two halves called connexon hemichannels. A connexon is a hexamer, meaning it is formed by six transmembrane connexin proteins. The six proteins arrange in a ring and create a pore in the center. One...

key terms and concepts

Learn how claudin, occludin, tricellulin, and JAM seal cells, control selective permeability, and support barriers like the blood-brain barrier.

Tight Junction Proteins and Cell Barriers | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Tight Junction Proteins and Cell Barriers

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