Name: how adherens junctions sense force
Uploaded: 2023-04-30T12:28:30.000Z
Duration: 1 min 26 s
Channel: JoVE

Gewebe wie die Haut und das Darmepithel sind ständig äußeren mechanischen Kräften wie Zwicken oder Dehnen ausgesetzt.
Die Adhärenzverbindungen, die diese Epithelzellen miteinander verankern, können sich als Reaktion auf eine solche mechanische Spannung dynamisch verändern. Diese Umwandlung von mechanischen Reizen in biochemische Veränderungen wird als Mechanotransduktion bezeichnet.
In diesen Zellen bilden die Adhärentenverbindungen eine durchgehende Bindungszone – den Adhäsionsgürtel – der aus großen Ansammlungen von Cadherinen, Cateninen und Aktomyosin-kontraktilen Bündeln besteht.
Die Alpha-Catenine an diesen Verbindungsstellen fungieren als mechanosensorische Proteine, die ihre Konformation als Reaktion auf mechanische Spannung ändern.
Wenn erhöhte kontraktile Kräfte an den Aktinfilamenten ziehen, wechselt das Alpha-Catenin von der gefalteten zur ungefalteten Konformation.
Diese Entfaltung öffnet eine kryptische Bindungsstelle an Vinculin, ein Bindungsprotein des Zytoskeletts, das in seiner geschlossenen, inaktiven Form im Zytoplasma verbleibt.
Nach der Bindung von Alpha-Catenin ändert Vinculin seine Konformation in seine offene, aktive Form.
Das aktive Vinculin fördert die Rekrutierung zusätzlicher Aktinfilamente an der Stelle, stärkt so die Verbindung und verteilt die Kraft auf die Zellen.

<ol>
	<li>Charras, Guillaume und Alpha S. Yap. "Zugkräfte und Mechanotransduktion an Zell-Zell-Verbindungen." Current Biology 28.8 (2018): R445-R457.</li>
	<li>Goldmann, Wolfgang H. "Die Rolle von Vinculin bei der zellulären Mechanotransduktion." Zellbiologie international 40.3 (2016): 241-256.</li>
	<li>Pinheiro, Diana und Yohanns Bellaiche. "Mechanisch kraftgetriebener Umbau von Adhärensverbindungen und Epitheldynamik." Entwicklungszelle 47.1 (2018): 3-19.</li>
</ol>

spannungsreaktion an adheren-kreuzungen

Tension Response at Adherens Junctions

Die adhärenten Verbindungen, die Zellen miteinander verankern, sind Multiproteinkomplexe, die sich dynamisch an mechanische Reize wie Zugkräfte und Scherbeanspruchung anpassen. Mechanosensorische Proteine in diesen Verbindungen können solche mechanischen Reize wahrnehmen und ihre Konformation verändern, was zu einer veränderten Funktion führt – ein Prozess, der Mechanotransduktion genannt wird.

α-Catenin als mechanosensorisches Protein

Das α-Catenin von Adherens Junctions ist ein allosterisches Protein mit drei VH-Domänen (Vinculin-Homologie), das verschiedene Aktin-bindende Proteine wie Vinculin, Afadin und α-Aktinin binden kann. Unter normalen Bedingungen ist das α-Catenin gefaltet und diese VH-Bindungsdomänen sind nicht zugänglich. Das N-terminale Ende ist an β-Catenin verankert und das C-terminale Ende ist an das Actomyosin-Zytoskelett gebunden. Wenn die innere Zugkraft zunimmt und Myosin II am Aktinfilament zieht, entfaltet sich das gebundene α-Catenin und seine VH-Domänen werden für die Bindung verfügbar.

Rolle von Vinculin bei der Mechanotransduktion

Vinculin ist ein weiteres dynamisches Protein mit einer Kopf- und einer Schwanzdomäne, die durch eine flexible Halsregion verbunden sind. In seiner inaktiven Form interagieren die Kopf- und Schwanzdomänen miteinander und verhindern so die Bindung anderer Proteine. Wenn jedoch die exponierte VH-Domäne von α-Catenin die Vinculin-Kopfdomäne bindet, ändert sich das Protein in eine offene Konformation. Die freie Schwanzdomäne kann nun Aktin binden und weitere Aktinfilamente an dieser Verbindung rekrutieren. Die offene Halsregion bindet auch verschiedene Proteine, die die Aktin-Polymerisation regulieren, wie z. B. Arp2/3, und organisiert so das Aktin-Zytoskelett als Reaktion auf mechanischen Stress dynamisch neu.

Spannungsreaktion an Adheren-Kreuzungen

Die Adhärensverbindungen, die die Zellen miteinander verankern, sind Multiproteinkomplexe, die sich dynamisch an mechanische Reize wie Zugkräfte und ...

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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 that can bind actin-binding proteins such as vinculin, afadin, and alpha-actinin. Under normal conditions, alpha-catenin is folded, so these VH binding domains stay hidden.

The N-terminal end of alpha-catenin is attached to beta-catenin. Its C-terminal end is linked to the actomyosin cytoskeleton. When internal tensile force increases, myosin II pulls on the actin filament. This pull makes alpha-catenin unfold. Once it opens, its VH domains become available for binding.

Vinculin also helps the junction respond to force. It has a head domain and a tail domain joined by a flexible neck region. In its inactive form, the head and tail interact with each other, which blocks other proteins from binding. When the exposed VH domain of alpha-catenin binds the vinculin head domain, vinculin changes into an open shape.

In the open form, vinculin can use its tail domain to bind actin and recruit more actin filaments to the junction. The open neck region can also bind proteins that control actin polymerization, such as Arp2/3. Together, these changes help reorganize the actin cytoskeleton in response to mechanical stress.

How Adherens Junctions Sense Force

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tension response at adherens junctions

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...

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key terms and concepts

Learn how adherens junctions use alpha-catenin and vinculin to sense tension, unfold, and reorganize actin during mechanotransduction.

How Adherens Junctions Sense Force | JoVE K12

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How Adherens Junctions Sense Force

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