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

皮膚や腸上皮などの組織は、つまんだり伸びたりするなどの外部の機械的な力を常に受けています。
これらの上皮細胞を一緒に固定する接着結合は、このような機械的張力に応答して動的に変化する可能性があります。この機械的刺激の生化学的変化への変換は、メカノトランスダクションと呼ばれます。
これらの細胞では、接着結合部が連続的な付着帯(接着ベルト)を形成し、カドヘリン、カテニン、およびアクトミオシンの収縮束の大きなクラスターで構成されています。
これらの接合部にあるα-カテニンは、機械的張力に応答してコンフォメーションを変化させる機械感覚タンパク質として機能します。
収縮力が増加するとアクチンフィラメントが引っ張られると、α-カテニンは折り畳まれた立体配座から折りたたまれた立体配座に変化します。
この展開により、細胞質に閉じた不活性な形で残る細胞骨格結合タンパク質であるビンキュリンへの不可解な結合部位が開かれます。
α-カテニンが結合すると、ビンキュリンはその開放的で活性な形態にコンフォメーションを変化させます。
活性ビンキュリンは、部位への追加のアクチンフィラメントの動員を促進し、接合部を強化し、細胞全体に力を分散させます。

<ol>
	<li>「細胞間接合部での引張力とメカノトランスダクション」 Current Biology 28.8 (2018): R445-R457.</li>
	<li>Goldmann, Wolfgang H. 「細胞メカノトランスダクションにおけるビンキュリンの役割」 Cell biology international 40.3 (2016): 241-256.</li>
	<li>「機械的な力駆動の接着体接合リモデリングと上皮ダイナミクス」 発生細胞 47.1 (2018): 3-19.</li>
</ol>

接着接合部における張力応答

Tension Response at Adherens Junctions

細胞を互いに固定する接着結合は、引張力やせん断応力などの機械的刺激に動的に適応する多タンパク質複合体です。 これらの接合部にある機械感覚タンパク質は、そのような機械的刺激を感知して構造の変化を起こし、その結果機能が変化します。これは機械伝達と呼ばれるプロセスです。

機械感覚タンパク質としてのα-カテニン

接着結合のα-カテニンは、ビンキュリン、アファジン、α-アクチニンなどのさまざまなアクチン結合タンパク質に結合できる 3 つの VH (ビンキュリン相同性) ドメインを持つアロステリックタンパク質です。 通常の条件下では、α-カテニンは折りたたまれており、これらの VH 結合ドメインにはアクセスできません。 N末端はβ-カテニンに固定されており、C末端はアクトミオシン細胞骨格に結合しています。 内部張力が増加し、ミオシン II がアクチン フィラメントを引っ張ると、結合していた α-カテニンが広がり、その VH ドメインが結合に利用できるようになります。

機械的伝達におけるビンキュリンの役割

ビンキュリンは、柔軟な首領域によって結合された頭部ドメインと尾部ドメインを備えた別の動的タンパク質です。 不活性型では、頭部ドメインと尾部ドメインが相互作用し、他のタンパク質の結合を防ぎます。 しかし、α-カテニンの露出した VH ドメインがビンキュリン頭部ドメインに結合すると、タンパク質は開いた立体構造に変化します。 自由尾部ドメインはアクチンに結合し、より多くのアクチン フィラメントをこの接合部に動員できるようになります。 オープンネック領域は、Arp2/3 などのアクチン重合を調節するさまざまなタンパク質にも結合し、機械的ストレスに応答してアクチン細胞骨格を動的に再構築します。

細胞を固定する接着結合は、引張力などの機械的刺激に動的に適応する多タンパク質複合体です。

Education

JoVE Core

Cell Biology

細胞生物学

Unit 1

ユニット1

Cell-Cell Interactions

細胞間相互作用

KEY TERMS AND CONCEPTS

主要用語と概念

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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catenins

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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

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immunoglobulin-like cell adhesion molecules

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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

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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 細胞生物学は、複雑な細胞プロセスを、わかりやすく包括的なアニメーション ビデオ レッスンで説明します。このコレクションは、細胞小器官や膜、細胞輸送、細胞のエネルギー学など、細胞の必須コンポーネントと機能に焦点を当てています。これは、実際の研究実験における細胞生物学の応用を実証する科学者による実際のビデオによって補足されています。

How Adherens Junctions Sense Force

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