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

Такие ткани, как кожа и кишечный эпителий, постоянно испытывают внешние механические силы, такие как сдавливание или растяжение.
Адгезивные соединения, которые связывают эти эпителиальные клетки вместе, могут динамически изменяться в ответ на такое механическое напряжение. Это преобразование механических стимулов в биохимические изменения называется механотрансдукцией.
В этих клетках адгезивные соединения образуют непрерывную зону прикрепления — пояс адгезии, состоящий из больших скоплений кадгеринов, катенинов и сократительных пучков актомиозина.
Альфа-катенины в этих соединениях действуют как механосенсорные белки, которые изменяют конформацию в ответ на механическое напряжение.
Когда повышенные сократительные силы тянут актиновые филаменты, альфа-катенин изменяется со складчатой на развернутую конформацию.
Это разворачивание открывает скрытый сайт связывания с винкулином, цитоскелетным связывающим белком, который остается в закрытой, неактивной форме в цитоплазме.
Связываясь с альфа-катенином, винкулин изменяет конформацию на открытую, активную форму.
Активный винкулин способствует привлечению дополнительных актиновых филаментов к участку, тем самым укрепляя соединение и распределяя силу по клеткам.

<ol>
	<li>Чаррас, Гийом и Альфа С. Яп. "Растягивающие силы и механотрансдукция на межклеточных соединениях." Current Biology 28.8 (2018): R445-R457.</li>
	<li>Гольдман, Вольфганг Х. "Роль винкулина в клеточной механотрансдукции." Международная клеточная биология 40.3 (2016): 241-256.</li>
	<li>Пиньейро, Диана и Йоханнс Беллайш. "Ремоделирование адгезивных соединений и эпителиальная динамика, вызванная механическим усилием." Клетка развития 47.1 (2018): 3-19.</li>
</ol>

Реакция на напряжение в адгерентных соединениях

Tension Response at Adherens Junctions

Адгерентные соединения, которые связывают клетки вместе, представляют собой мультибелковые комплексы, которые динамически адаптируются к механическим стимулам, таким как силы растяжения и напряжение сдвига. Механосенсорные белки в этих соединениях могут воспринимать такие механические стимулы и претерпевать сдвиг в своей конформации, что приводит к изменению функции — процесс, называемый механотрансдукцией. α-Катенин как механосенсорный белок α-катенин адгерентных соединений представляет собой аллостерический белок с тремя доменами VH (гомология винкулина), которые могут связывать различные актин-связывающие белки, такие как винкулин, афадин и α-актинин. В нормальных условиях α-катенин свернут, и эти связывающие домены VH недоступны. N-конец прикреплен к β-катенину, а С-конец связан с актомиозиновым цитоскелетом. Когда внутренняя сила растяжения увеличивается и миозин II тянет актиновую нить, связанный α-катенин разворачивается, и его домены VH становятся доступными для связывания. Роль винкулина в механотрансдукции Винкулин — еще один динамический белок с головным и хвостовым доменами, соединенными гибкой шейкой. В неактивной форме головной и хвостовой домены взаимодействуют друг с другом, предотвращая связывание других белков. Однако когда обнаженный VH-домен α-катенина связывается с головным доменом винкулина, белок меняется на открытую конформацию. Домен свободного хвоста теперь может связывать актин и привлекать к этому соединению больше актиновых нитей. Область открытой шейки также связывает различные белки, которые регулируют полимеризацию актина, такие как Arp2/3, тем самым динамически реорганизуя актиновый цитоскелет в ответ на механический стресс.

Адгезивные соединения, которые связывают клетки вместе, представляют собой многобелковые комплексы, которые динамически адаптируются к механическим раздражителям, таким как растягивающие силы и ...

Education

JoVE Core

Cell Biology

Клеточная биология

Unit 1

Раздел 1

Cell-Cell Interactions

Межклеточные взаимодействия

KEY TERMS AND CONCEPTS

ОСНОВНЫЕ ТЕРМИНЫ И ПОНЯТИЯ

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

cell adhesion molecules - types and functions

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Cell Adhesion Molecules in Tissues

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Cadherins in Cell Junctions and Disease

Cadherins are cell adhesion proteins that help cells stick together and build tissues. Their name comes from their calcium-dependent binding. Early examples were named E-cadherin, P-cadherin, and N-cadherin after the epithelial, placental, and neuronal cells where they were first found. Classical cadherins share similar sequences and structures. Other cadherins, including those involved in cell signaling, are grouped as non-classical cadherins. This diversity comes from multiple cadherin genes...

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Cadherins help cells sort into the right tissues during development. They are a large superfamily of cell adhesion molecules, with more than 180 variants. Different tissues express specific cadherin combinations, which helps cells recognize and stick to the right neighbors. Cadherins usually bind to the same or a closely related cadherin on another cell. This is called homophilic binding. Because of this matching behavior, cells of the same type tend to group together and form clusters that...

catenins

Catenins in Cell Junctions and Signaling

Catenins help cells stay connected and also support signaling inside the body. These proteins act as linker proteins in cell junction complexes because they have multiple binding domains and flexible structures. Most catenins contain a protein sequence called the armadillo repeat, so they are also known as armadillo proteins. Alpha-catenin is the main exception. Catenins bind to cell adhesion molecules such as cadherins. They then connect cadherins to cytoskeletal proteins, and the exact link...

selectins

Selectins in Immune Cell Capture

Selectins help cells make short, temporary contacts during immune responses. They are cell adhesion molecules that bind carbohydrate ligands on other cells. These rod-like proteins have a long outside region and end in a lectin domain, which binds carbohydrates only when calcium ions are present. Three main selectins are known: L-selectin, P-selectin, and E-selectin. Their names reflect where they are found and how long they are. This tissue specificity helps explain why selectins act in...

immunoglobulin-like cell adhesion molecules

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Ig-CAMs, or immunoglobulin-like cell adhesion molecules, are cell surface glycoproteins in the immunoglobulin superfamily. They contain immunoglobulin domains, and some also have fibronectin type III domains. Their Ig domains can be glycosylated to different degrees. These molecules can bind to the same kind of Ig-CAM or to other ligands, such as integrins. Most Ig-CAMs help cells stick together only for a short time. The nectin class is different because it helps form stable junctions,...

overview of cell-cell junctions

Cell Junctions in Tissues

Cell junctions help hold tissues together and let neighboring cells communicate. In multicellular organisms, the three-dimensional shape of tissues depends on interactions between cells and the extracellular matrix. Cell-cell junctions are specialized structures made of multi-protein complexes on one cell that connect with similar complexes on another cell. These junctions are grouped into three main types based on function: occluding, anchoring, and gap junctions. Tight junctions, also called...

adherens junctions

Cell Adhesion in Tissues and Infection

Adherens junctions are strong cell-to-cell anchors that help tissues stay connected. These anchoring junctions work with desmosomes, another type of junction that holds adjacent cells together. In many epithelial and endothelial tissues, adherens junctions form a continuous adhesion belt. In heart muscle, they often appear as clusters that help cells work together for coordinated contraction. Adherens junctions are also dynamic, especially in the cells that line blood vessels. These...

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...

desmosomes

Desmosomes and Cell Anchoring

Desmosomes are cell junctions that anchor cells together. They are button-like structures that create an interlinked network of intermediate filaments across cells. This strong link helps tissues resist mechanical stress and maintain tissue integrity. Desmosomes are built from multiple proteins. Their core includes desmosomal cadherins, which are adhesion proteins that bind to cadherins on neighboring cells. The two desmosomal cadherins are desmogleins and desmocollins. These transmembrane...

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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...

gap junctions

Cell Communication Through Gap Junctions

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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 Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

How Adherens Junctions Sense Force

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