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

피부와 장 상피와 같은 조직은 꼬집거나 늘어나는 것과 같은 외부의 기계적 힘을 지속적으로 경험합니다.
이러한 상피 세포를 함께 고정하는 부착 접합부는 이러한 기계적 장력에 반응하여 동적으로 변화할 수 있습니다. 기계적 자극을 생화학적 변화로 변환하는 것을 메카노트랜스덕션(mechanotransduction)이라고 합니다.
이러한 세포에서 adherens junctions는 cadherins, catenins 및 actomyosin contractile bundles의 큰 클러스터로 구성된 연속적인 부착 영역(adhesion belt)을 형성합니다.
이 접합부에 있는 알파-카테닌은 기계적 장력에 반응하여 형태를 변화시키는 기계감각 단백질로 작용합니다.
증가된 수축력이 액틴 필라멘트를 당기면 알파-카테닌은 접힌 형태에서 펼쳐진 형태로 바뀝니다.
이 풀림은 세포질에서 폐쇄되고 비활성 형태로 남아 있는 세포골격 결합 단백질인 빈쿨린(vinculin)에 대한 비밀스러운 결합 부위를 엽니다.
알파-카테닌과 결합하면 빈쿨린은 개방적이고 활동적인 형태로 형태가 바뀝니다.
활성 빈큘린은 부위에 추가적인 액틴 필라멘트의 동원을 촉진하여 접합부를 강화하고 세포에 힘을 분산시킵니다.

<ol>
	<li>Charras, Guillaume 및 Alpha S. Yap. "세포-세포 접합부에서의 인장력 및 기계 전달." Current Biology 28.8 (2018): R445-R457.</li>
	<li>Goldmann, Wolfgang H. "세포 메카노트랜스덕션에서 빈쿨린의 역할." Cell biology international 40.3 (2016): 241-256.</li>
	<li>Pinheiro, Diana, Yohanns Bellaiche. "기계적 힘 구동 접착 접합 리모델링 및 상피 역학." 발달 셀 47.1 (2018): 3-19.</li>
</ol>

부착연접의 장력 응답

Tension Response at Adherens Junctions

세포를 함께 고정시키는 부착연접은 인장력 및 전단 응력과 같은 기계적 자극에 동적으로 적응하는 다중 단백질 복합체입니다. 이러한 접합부의 기계감각 단백질은 이러한 기계적 자극을 감지하고 구조의 변화를 겪어 기능이 변경될 수 있습니다. 이 과정을 기계신호전달이라고 합니다.

기계감각 단백질로서의 α-카테닌

접착 접합부의 α-카테닌은 빈쿨린, 아파딘, α-액티닌과 같은 다양한 액틴 결합 단백질과 결합할 수 있는 3개의 VH(빈쿨린 상동성) 도메인을 가진 알로스테릭 단백질입니다. 정상적인 조건에서는 α-카테닌이 접혀 있어 이러한 VH 결합 도메인에 접근할 수 없습니다. N 말단은 β-카테닌에 고정되어 있고 C 말단은 액토미오신 세포골격에 결합되어 있습니다. 내부 인장력이 증가하고 미오신 II가 액틴 필라멘트를 잡아당기면 결합된 α-카테닌이 풀리고 VH 도메인이 결합할 수 있게 됩니다.

기계신호전달에서 빈쿨린의 역할

빈쿨린은 머리와 꼬리 영역이 유연한 목 부분으로 연결된 또 다른 동적 단백질입니다. 비활성 형태에서는 머리와 꼬리 도메인이 서로 상호작용하여 다른 단백질의 결합을 방지합니다. 그러나 α-카테닌의 노출된 VH 도메인이 빈쿨린 헤드 도메인과 결합하면 단백질은 열린 형태로 변경됩니다. 자유 꼬리 도메인은 이제 액틴을 결합하고 이 접합부에 더 많은 액틴 필라멘트를 모집할 수 있습니다. 열린 목 영역은 또한 Arp2/3과 같은 액틴 중합을 조절하는 다양한 단백질과 결합하여 기계적 스트레스에 반응하여 액틴 세포골격을 동적으로 재구성합니다.

세포를 함께 고정하는 부착 접합부는 인장력 및 ...

Education

교육

JoVE Core

Cell Biology

세포생물학

Unit 1

제1단원

Cell-Cell Interactions

세포 간 상호작용

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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

cell-adhesion-molecules-types-and-functions

Cell Adhesion Molecules in Tissues

Cell adhesion molecules help cells stick together and work as part of a tissue. They give multicellular organisms physical strength and also help cells send signals across the plasma membrane. These proteins are important for coordinated activity in tissues and organ systems. CAMs are grouped into four main families: integrins, cadherins, selectins, and immunoglobulin-like CAMs, or IgCAMs. Each family supports cell interactions in a different way. Some CAMs help cells attach firmly, while...

structure of cadherins

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...

cadherins in tissue organization

Cadherins Guide Cell Sorting in Tissues

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

immunoglobulin-like-cell-adhesion-molecules

Ig-CAMs in Neural Growth and Disease

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...

tight junctions

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

Gap junctions let adjacent animal cells share small molecules, ions, and secondary messengers. These communication channels connect the cytoplasm of neighboring cells. They are built from many molecular channels, often from a few hundred to thousands in one junction. Each channel is made of two halves called connexon hemichannels. A connexon is a hexamer, meaning it is formed by six transmembrane connexin proteins. The six proteins arrange in a ring and create a pore in the center. One...

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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