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

Tkanki, takie jak skóra i nabłonek jelitowy, są stale narażone na zewnętrzne siły mechaniczne, takie jak szczypanie lub rozciąganie.
Połączenia adherenowe, które zakotwiczają te komórki nabłonkowe razem, mogą się dynamicznie zmieniać w odpowiedzi na takie napięcie mechaniczne. Ta konwersja bodźców mechanicznych na zmiany biochemiczne nazywa się mechanotransdukcją.
W tych komórkach połączenia adherenów tworzą ciągłą strefę przyczepu — pas adhezyjny — składającą się z dużych skupisk kadheryny, kateniny i wiązek kurczliwych aktomiozyny.
Alfa-kateniny w tych połączeniach działają jak białka mechanosensoryczne, które zmieniają konformację w odpowiedzi na napięcie mechaniczne.
Kiedy zwiększone siły kurczliwe ciągną włókna aktynowe, alfa-katenina zmienia się z konformacji złożonej na rozłożoną.
To rozwijanie otwiera tajemnicze miejsce wiązania z winkuliną, białkiem wiążącym cytoszkielet, które pozostaje w swojej zamkniętej, nieaktywnej postaci w cytoplazmie.
Po związaniu alfa-kateniny winkulina zmienia konformację do otwartej, aktywnej formy.
Aktywna winkulina wspomaga rekrutację dodatkowych włókien aktyny do tego miejsca, wzmacniając w ten sposób połączenie i rozprowadzając siłę po komórkach.

<ol>
	<li>Charras, Guillaume i Alpha S. Yap. "Siły rozciągające i mechanotransdukcja na połączeniach komórka-komórka". Aktualna biologia 28.8 (2018): R445-R457.</li>
	<li>Goldmann, Wolfgang H. "Rola winkuliny w mechanotransdukcji komórkowej." Międzynarodowa Biologia Komórki 40.3 (2016): 241-256.</li>
	<li>Pinheiro, Diana i Yohanns Bellaiche. "Mechaniczna przebudowa połączeń przylegających do siły mechanicznej i dynamika nabłonka". Komórka rozwojowa 47.1 (2018): 3-19.</li>
</ol>

reakcja na napięcie na skrzyżowaniach adheren

Tension Response at Adherens Junctions

Połączenia przylegające, które zakotwiczają razem komórki, to kompleksy wielobiałkowe, które dynamicznie dostosowują się do bodźców mechanicznych, takich jak siły rozciągające i naprężenia ścinające. Białka mechanosensoryczne w tych połączeniach potrafią wyczuwać takie bodźce mechaniczne i ulegają zmianie w swojej konformacji, co skutkuje zmianą funkcji – procesem zwanym mechanotransdukcją. α-katenina jako białko mechanosensoryczne α-katenina połączeń przylegających jest białkiem allosterycznym z trzema domenami VH (homologia winkuliny), które mogą wiązać różne białka wiążące aktynę, takie jak winkulina, afadyna i α-aktynina. W normalnych warunkach α-katenina jest zwinięta i domeny wiążące VH są niedostępne. N-koniec jest zakotwiczony do β-kateniny, a C-koniec jest związany z cytoszkieletem aktomiozyny. Kiedy wewnętrzna siła rozciągająca wzrasta i miozyna II ciągnie za włókno aktynowe, związana α-katenina rozwija się, a jej domeny VH stają się dostępne do wiązania. Rola winkuliny w mechanotransdukcji Winkulina to kolejne dynamiczne białko z domeną głowy i ogona połączone elastycznym obszarem szyi. W swojej nieaktywnej formie domeny głowy i ogona oddziałują ze sobą, zapobiegając wiązaniu się innych białek. Jednakże, gdy odsłonięta domena VH α-kateniny wiąże się z domeną główną winkuliny, białko zmienia się w konformację otwartą. Domena wolnego ogona może teraz wiązać aktynę i rekrutować więcej włókien aktynowych do tego połączenia. Region otwartej szyi wiąże również różne białka regulujące polimeryzację aktyny, takie jak Arp2/3, dynamicznie reorganizując w ten sposób cytoszkielet aktynowy w odpowiedzi na naprężenia mechaniczne.

Reakcja na napięcie na skrzyżowaniach Adheren

Połączenia adherenowe, które zakotwiczają komórki razem, to kompleksy wielobiałkowe, które dynamicznie dostosowują się do bodźców mechanicznych, takich jak siły rozciągające i ...

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JoVE Core

Cell Biology

Biologia komórki

Unit 1

Jednostka 1

Cell-Cell Interactions

Interakcje międzykomórkowe

KEY TERMS AND CONCEPTS

Kluczowe terminy i pojęcia

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

cell biology

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How Adherens Junctions Sense Force

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