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

Les tissus tels que la peau et l’épithélium intestinal subissent constamment des forces mécaniques externes telles que le pincement ou l’étirement.
Les jonctions adhérentes qui ancrent ces cellules épithéliales ensemble peuvent changer dynamiquement en réponse à une telle tension mécanique. Cette conversion des stimuli mécaniques en changements biochimiques est appelée mécanotransduction.
Dans ces cellules, les jonctions adhérentes forment une zone continue d’attachement – la ceinture d’adhésion – comprenant de grands amas de faisceaux contractiles de cadhérines, de caténines et d’actomyosine.
Les alpha-caténines à ces jonctions agissent comme des protéines mécanosensorielles qui changent de conformation en réponse à la tension mécanique.
Lorsque des forces contractiles accrues tirent les filaments d’actine, l’alpha-caténine passe de la conformation pliée à la conformation dépliée.
Ce dépliage ouvre un site de liaison cryptique à la vinculine, une protéine de liaison du cytosquelette qui reste sous sa forme fermée et inactive dans le cytoplasme.
Lors de la liaison de l’alpha-caténine, la vinculine change de conformation pour devenir sa forme ouverte et active.
La vinculine active favorise le recrutement de filaments d’actine supplémentaires sur le site, renforçant ainsi la jonction et répartissant la force sur les cellules.

<ol>
	<li>Charras, Guillaume et Alpha S. Yap. « Forces de traction et mécanotransduction aux jonctions cellule-cellule. » Current Biology 28.8 (2018) : R445-R457.</li>
	<li>Goldmann, Wolfgang H. « Rôle de la vinculine dans la mécanotransduction cellulaire. » Biologie cellulaire internationale 40.3 (2016) : 241-256.</li>
	<li>Pinheiro, Diana et Yohanns Bellaiche. « Remodelage de la jonction adhérente et dynamique épithéliale entraînés par la force mécanique. » Cellule développementale 47.1 (2018) : 3-19.</li>
</ol>

réponse à la tension aux jonctions adhérentes

Tension Response at Adherens Junctions

Les jonctions adhérentes qui ancrent les cellules ensemble sont des complexes multiprotéiques qui s'adaptent dynamiquement aux stimuli mécaniques tels que les forces de traction et les contraintes de cisaillement. Les protéines mécanosensorielles de ces jonctions peuvent détecter de tels stimuli mécaniques et subir un changement de conformation, entraînant une modification de leur fonction - un processus appelé mécanotransduction.

L'α-caténine en tant que protéine mécanosensorielle

L'α-caténine des jonctions adhérentes est une protéine allostérique avec trois domaines VH (homologie de la vinculine) qui peuvent se lier à diverses protéines de liaison à l'actine comme la vinculine, l'afadine et l'α-actinine. Dans des conditions normales, l’α-caténine est repliée et ces domaines de liaison au VH sont inaccessibles. L'extrémité N-terminale est ancrée à la β-caténine et l'extrémité C-terminale est liée au cytosquelette d'actomyosine. Lorsque la force de traction interne augmente et que la myosine II tire sur le filament d'actine, l'α-caténine liée se déplie et ses domaines VH deviennent disponibles pour la liaison.

Rôle de la Vinculine dans la Mécanotransduction

La vinculine est une autre protéine dynamique avec un domaine de tête et un domaine de queue reliés par une région de cou flexible. Dans sa forme inactive, les domaines de tête et de queue interagissent les uns avec les autres, empêchant la liaison d'autres protéines. Cependant, lorsque le domaine VH exposé de l’α-caténine se lie au domaine de tête de la vinculine, la protéine prend une conformation ouverte. Le domaine de queue libre peut désormais lier l'actine et recruter davantage de filaments d'actine à cette jonction. La région du col ouvert lie également diverses protéines qui régulent la polymérisation de l'actine, telles que Arp2/3, réorganisant ainsi dynamiquement le cytosquelette d'actine en réponse au stress mécanique.

Réponse à la Tension aux Jonctions Adhérentes

Les jonctions adhérentes qui ancrent les cellules ensemble sont des complexes multiprotéiques qui s’adaptent dynamiquement à des stimuli mécaniques tels que les forces de traction et ...

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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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