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

Los tejidos, como la piel y el epitelio intestinal, experimentan constantemente fuerzas mecánicas externas, como pellizcos o estiramientos.
Las uniones adherentes que unen estas células epiteliales pueden cambiar dinámicamente en respuesta a dicha tensión mecánica. Esta conversión de estímulos mecánicos en cambios bioquímicos se denomina mecanotransducción.
En estas células, las uniones adherentes forman una zona continua de unión, el cinturón de adhesión, que comprende grandes grupos de cadherinas, cateninas y haces contráctiles de actomiosina.
Las alfa-cateninas en estas uniones actúan como proteínas mecanosensoriales que cambian de conformación en respuesta a la tensión mecánica.
Cuando el aumento de las fuerzas contráctiles tira de los filamentos de actina, la alfa-catenina cambia de la conformación plegada a la desplegada.
Este despliegue abre un sitio de unión críptico a la vinculina, una proteína de unión al citoesqueleto que permanece en su forma cerrada e inactiva en el citoplasma.
Al unirse a la alfa-catenina, la vinculina cambia de conformación a su forma abierta y activa.
La vinculina activa promueve el reclutamiento de filamentos de actina adicionales al sitio, fortaleciendo así la unión y distribuyendo la fuerza a través de las células.

<ol>
	<li>Charras, Guillaume y Alpha S. Yap. "Fuerzas de tracción y mecanotransducción en uniones célula-célula". Current Biology 28.8 (2018): R445-R457.</li>
	<li>Goldmann, Wolfgang H. "Papel de la vinculina en la mecanotransducción celular". Biología celular internacional 40.3 (2016): 241-256.</li>
	<li>Pinheiro, Diana y Yohanns Bellaiche. "La remodelación de la unión y la dinámica epitelial impulsadas por la fuerza mecánica se adhieren a la mígelia". Célula de desarrollo 47.1 (2018): 3-19.</li>
</ol>

respuesta a la tensión en las uniones adheren

Tension Response at Adherens Junctions

Las uniones adherentes que anclan las células son complejos multiproteicos que se adaptan dinámicamente a estímulos mecánicos como fuerzas de tracción y esfuerzos cortantes. Las proteínas mecanosensoriales en estas uniones pueden detectar tales estímulos mecánicos y sufrir un cambio en su conformación, lo que resulta en una función alterada, un proceso llamado mecanotransducción.

α-catenina como proteína mecanosensorial

La α-catenina de las uniones adherentes es una proteína alostérica con tres dominios VH (homología de vinculina) que pueden unirse a varias proteínas de unión a actina como vinculina, afadina y α-actinina. En condiciones normales, la α-catenina está plegada y estos dominios de unión a VH son inaccesibles. El extremo N-terminal está anclado a la β-catenina y el extremo C-terminal está unido al citoesqueleto de actomiosina. Cuando la fuerza de tracción interna aumenta y la miosina II tira del filamento de actina, la α-catenina unida se despliega y sus dominios VH quedan disponibles para su unión.

Papel de la vinculina en la mecanotransducción

La vinculina es otra proteína dinámica con un dominio de cabeza y cola unidos por una región de cuello flexible. En su forma inactiva, los dominios de cabeza y cola interactúan entre sí, impidiendo la unión de otras proteínas. Sin embargo, cuando el dominio VH expuesto de la α-catenina se une al dominio de la cabeza de vinculina, la proteína cambia a una conformación abierta. El dominio de la cola libre ahora puede unirse a actina y reclutar más filamentos de actina para esta unión. La región del cuello abierto también se une a varias proteínas que regulan la polimerización de actina, como Arp2/3, reorganizando así dinámicamente el citoesqueleto de actina en respuesta al estrés mecánico.

Respuesta a la tensión en las uniones Adheren

Las uniones adherentes que unen las células son complejos multiproteicos que se adaptan dinámicamente a estímulos mecánicos como las fuerzas de tracción y ...

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Cell Biology

Biología Celular

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Cell-Cell Interactions

Interacciones célula-célula

KEY TERMS AND CONCEPTS

TÉRMINOS Y CONCEPTOS CLAVE

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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Desmosomes and Cell Anchoring

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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

cell biology

JoVE Core Biología Celular ilustra procesos celulares complejos mediante completos vídeos animados fáciles de entender. Esta colección se centra en los componentes esenciales de las células y su funcionamiento, incluyendo los orgánulos y las membranas, el transporte celular y el metabolismo energético celular. Todo este material se complementa con los vídeos de científicos en acción, que muestran la aplicación de la biología celular en experimentos reales de investigación.

How Adherens Junctions Sense Force

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