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

In Organen wie Niere und Darm sind die Epithelzellen mit Tight Junctions verschlossen, um den Fluss von Makromolekülen, Ionen und kleinen gelösten Stoffen durch den parazellulären Raum zu verhindern.
Tight Junctions bestehen hauptsächlich aus Claudin- und Occludin-Transmembranproteinen mit jeweils vier membranüberspannenden alpha-Helices.
Reihen von Claudinen und Occludinen polymerisieren auf der Membran und bilden ein Netzwerk aus Dichtungssträngen.
Diese Stränge heften sich durch ihre extrazellulären Schleifen an ähnliche Proteinstränge auf der Nachbarzelle und halten so die beiden Membranen zusammen.
Auf der zytoplasmatischen Seite assoziieren die C-terminalen Schwänze dieser Proteine mit den PDZ-Domänen großer Gerüstproteine, die als Zonula occludens oder ZO bezeichnet werden.
Die ZO-Proteine haben mehrere Proteinbindungsdomänen und können so Claudine, Occludine, Aktin und andere ZO-Proteine binden und ein Netz bilden, das diese Dichtungsstränge organisiert und stabilisiert.
Tight Junctions verschließen nicht nur den parazellulären Raum, sondern verhindern auch die laterale Bewegung von Proteinen, wie z. B. Glukosetransportern, entlang der Membran. Dies hilft, diese Proteine auf der apikalen Oberfläche des Darmepithels zu lokalisieren, um die Glukoseaufnahme zu ermöglichen.

<ol>
	<li>Sawada, Norimasa. "Tight Junction-bedingte menschliche Krankheiten." Pathologie international 63.1 (2013): 1-12. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168075/">Verknüpfung</a></li>
	<li>Anderson, James M. und Christina M. Van Itallie. "Physiologie und Funktion der Tight Junction." Perspektiven des Cold Spring Harbor in der Biologie 1.2 (2009): a002584. <a href="https://cshperspectives.cshlp.org/content/1/2/a002584.full">Verknüpfung</a></li>
	<li>Mariano, Cibelle, et al. "Ein Blick auf Tricellulin und seine Rolle bei der Bildung und Aufrechterhaltung von Tight Junctions." Europäische Zeitschrift für Zellbiologie 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>

enge Übergänge

Tight Junctions

Tight Junctions sind molekulare Versiegelungen zwischen Zellen, die das Austreten von Flüssigkeiten, Ionen und anderen kleinen gelösten Substanzen  durch Hohlräume und Kompartimente in mehrzelligen Organismen verhindern. Sie bestehen hauptsächlich aus Claudin- und Occludin-Transmembranproteinen sowie anderen Proteinen wie Tricellulin und JAM (Junctional Adhäsionsmolekül). Alle diese Proteine sind 4-Pass-Transmembranproteine, mit Ausnahme von JAM, einem Single-Pass-Transmembranprotein, das zur Immunglobulin-Superfamilie gehört. Die extrazellulären Domänen dieser Tight-Junction-Proteine interagieren mit denen auf der angrenzenden Zellmembran und bringen so die beiden benachbarten Zellen zusammen und versiegeln sie.

Selektive Durchlässigkeit dichter Verbindungen

Es gibt mehrere Isoformen des Transmembran-Claudins, wobei beim Menschen bis zu 24 verschiedene Typen exprimiert werden. Die Diversität des Claudin-Proteins verleiht verschiedenen Tight Junctions selektive Permeabilität. Beispielsweise erhöht Claudin-16, das im Nierenepithel exprimiert wird, die Durchlässigkeit für Magnesiumionen und ermöglicht so deren Wiederaufnahme aus dem Blut während der Filtration. Im Gegensatz dazu verringert das in den Endothelzellen der Gehirnkapillaren exprimierte Claudin-5 selektiv die Ionenpermeabilität über die Blut-Hirn-Schranke hinweg.

Dreizellige Verbindungen

Tight Junctions dichten nicht nur Lücken zwischen zwei Zellen ab, sondern dichten auch die Lücken ab, die an der Verbindung von drei Zellen entstehen – einer trizellulären Verbindung. Die Struktur trizellulärer Verbindungen wurde erstmals in den 1970er Jahren mithilfe der Gefrierbruch-Elektronenmikroskopie beobachtet. An diesen Verbindungsstellen sind die Dichtungsstränge senkrecht zu den Strängen der bizellulären Tight Junctions ausgerichtet. Der trizelluläre Kontaktpunkt bildet somit eine schmale vertikale Röhre mit einem Durchmesser von etwa 10 nm, die die parazelluläre Bewegung von Molekülen steuert.

Tricellulin war das erste Protein, das sich an diesen trizellulären Verbindungen konzentrierte. Es weist Sequenzhomologie mit den Occludin-Proteinen auf und weist beim Menschen vier Isoformen auf. Interessanterweise führen Mutationen im Tricellulin-Gen (TRIC) nachweislich zu einer Beeinträchtigung des Hörvermögens, was seine Bedeutung für die Aufrechterhaltung eines dichten Verschlusses zeigt, wie er beispielsweise im Corti-Organ – einer Struktur im Innenohr – erforderlich ist.

Enge Übergänge

Tight Junctions sind molekulare Dichtungen zwischen Zellen, die das Austreten von Flüssigkeiten, Ionen und anderen kleinen gelösten Stoffen durch Hohlräume und Kompartimente in ...

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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.

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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 Zellbiologie veranschaulicht komplexe zelluläre Prozesse in leicht verständlichen und dennoch umfassenden animierten Videolektionen. Diese Sammlung konzentriert sich auf die wesentlichen Bestandteile und Funktionen von Zellen, einschließlich Organellen und Membranen, Zelltransport und Zellenergie. Ergänzt wird sie durch Videos von Wissenschaftlern in Aktion, die die Anwendung der Zellbiologie in realen Forschungsexperimenten demonstrieren.

Tight Junction Proteins and Cell Barriers

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