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

Tessuti come la pelle e l'epitelio intestinale subiscono costantemente forze meccaniche esterne come pizzicamento o stiramento.
Le giunzioni aderenti che ancorano insieme queste cellule epiteliali possono cambiare dinamicamente in risposta a tale tensione meccanica. Questa conversione di stimoli meccanici in cambiamenti biochimici è chiamata meccanotrasduzione.
In queste cellule, le giunzioni aderenti formano una zona continua di attaccamento, la cintura di adesione, che comprende grandi gruppi di caderine, catenine e fasci contrattili di actomiosisina.
Le alfa-catenine in queste giunzioni agiscono come proteine meccanosensoriali che cambiano conformazione in risposta alla tensione meccanica.
Quando l'aumento delle forze contrattili tira i filamenti di actina, l'alfa-catenina cambia dalla conformazione ripiegata a quella dispiegata.
Questo dispiegamento apre un sito di legame criptico alla vinculina, una proteina legante il citoscheletro che rimane nella sua forma chiusa e inattiva nel citoplasma.
Dopo aver legato l'alfa-catenina, la vinculina cambia conformazione nella sua forma aperta e attiva.
La vinculina attiva promuove il reclutamento di ulteriori filamenti di actina nel sito, rafforzando così la giunzione e distribuendo la forza attraverso le cellule.

<ol>
	<li>Charras, Guillaume e Alpha S. Yap. "Forze di trazione e meccanotrasduzione alle giunzioni cellula-cellula". Current Biology 28.8 (2018): R445-R457.</li>
	<li>Goldmann, Wolfgang H. "Ruolo della vinculina nella meccanotrasduzione cellulare". Biologia cellulare internazionale 40.3 (2016): 241-256.</li>
	<li>Pinheiro, Diana e Yohanns Bellaiche. "La forza meccanica aderisce al rimodellamento della giunzione e alla dinamica epiteliale". Cellula di sviluppo 47.1 (2018): 3-19.</li>
</ol>

risposta alla tensione delle giunzioni aderenti

Tension Response at Adherens Junctions

Le giunzioni aderenti che ancorano insieme le cellule sono complessi multiproteici che si adattano dinamicamente agli stimoli meccanici come le forze di trazione e lo stress di taglio. Le proteine meccano-sensoriali in queste giunzioni possono percepire tali stimoli meccanici e subire un cambiamento nella loro conformazione, risultando in una funzione alterata – un processo chiamato meccanotrasduzione.

α-catenina come proteina meccano-sensoriale

L'α-catenina delle giunzioni aderenti è una proteina allosterica con tre domini VH (omologia vinculina) che possono legare varie proteine leganti l'actina come vinculina, afadina e α-actinina. In condizioni normali, l'α-catenina è ripiegata e questi domini di legame VH sono inaccessibili. L'estremità N-terminale è ancorata alla β-catenina e l'estremità C-terminale è legata al citoscheletro dell'actomiosina. Quando la forza di tensione interna aumenta e la miosina II tira il filamento di actina, l’α-catenina legata si dispiega e i suoi domini VH diventano disponibili per il legame.

Ruolo della Vinculina nella meccanotrasduzione

La vinculina è un'altra proteina dinamica con un dominio di testa e uno di coda uniti da una regione flessibile del collo. Nella sua forma inattiva, i domini della testa e della coda interagiscono tra loro, impedendo il legame di altre proteine. Tuttavia, quando il dominio VH esposto dell'α-catenina si lega al dominio della testa della vinculina, la proteina cambia in una conformazione aperta. Il dominio della coda libera può ora legarsi all'actina e reclutare più filamenti di actina a questa giunzione. La regione del collo aperto lega anche varie proteine che regolano la polimerizzazione dell'actina, come Arp2/3, riorganizzando così dinamicamente il citoscheletro di actina in risposta allo stress meccanico.

Risposta alla tensione delle giunzioni aderenti

Le giunzioni aderenti che ancorano le cellule insieme sono complessi multiproteici che si adattano dinamicamente a stimoli meccanici come le forze di trazione e ...

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JoVE Core

Cell Biology

Biologia cellulare

Unit 1

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Cell-Cell Interactions

Interazioni cellula-cellula

KEY TERMS AND CONCEPTS

TERMINI E CONCETTI CHIAVE

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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