Name: desmosomes and cell anchoring
Uploaded: 2025-05-22T09:05:46.000Z
Duration: 1 min 5 s
Channel: JoVE

デスモソームは、心筋や腸上皮など、機械的ストレスを受ける組織に多く見られる固定接合部です。
デスモソームでの細胞接着は、デスモソームカドヘリン、すなわちデスモコリンとデスモグレインによって促進され、これらはそれらの細胞外ドメインの不均一性相互作用を介して接着します。
カドヘリンの細胞質ドメインは、プラコグロビンと呼ばれるカテニンとプラコフィリンと結合し、細胞質側に密なプラークを形成します。
カテニンは中間フィラメントに直接結合することはできず、プラキンファミリーに属する細胞骨格リンカータンパク質であるデスモプラキンによってそれらに結合されています。
デスモプラキンのN末端ドメインはカテニンに結合し、それらのC末端プラキンリピートは中間フィラメントに結合します。
したがって、デスモソームは隣接する細胞の中間フィラメントを固定し、組織全体に経細胞細胞骨格ネットワークを形成します。

<ol>
	<li>Delva、Emmanuella、Dana K. Tucker、Andrew P. Kowalczyk. 「デスモソーム」 Cold Spring Harbor perspectives in biology 1.2 (2009): a002543.</li>
	<li>「デスモソームの構造、組成および機能」 Biochimica et Biophysica Acta (BBA)-Biomembranes 1778.3 (2008): 572-587.</li>
	<li>「デスモソームの集合とダイナミクス」 細胞生物学の動向 23.11 (2013): 537-546.</li>
</ol>

デスモソーム

Desmosomes

デスモソームという用語は、ギリシャ語の「デスモ」と「接着体」を意味する「ソーマ」に由来しています。 この構造は 1800 年代後半に初めて観察され、表皮にある小さくて密な結節として説明されました。 デスモソームはボタンのような構造で、細胞全体に中間フィラメントの相互結合ネットワークを形成するのに役立ちます。 これらの接合部は、機械的ストレス下で細胞を保持し、組織の完全性を維持するために不可欠です。 デスモソームは、さまざまなアダプタータンパク質を介して中間フィラメントに結合したデスモソームカドヘリンを含む複数タンパク質複合体です。

デスモソームカドヘリン

カドヘリンはデスモソームの細胞外コア領域を形成し、隣接する細胞上のカドヘリンに結合します。 デスモソームには、デスモグレインとデスモコリンという 2 種類のカドヘリンがあります。 これらの膜貫通糖タンパク質は、4 つのカドヘリンリピートと、これらのタンパク質を細胞膜に固定する 1 つの細胞外アンカードメインを含む大きな細胞外部分を持っています。 デスモグレインとデスモコリンのヘテロ二量体ペアは、同じ細胞上のシス相互作用および隣接する細胞間のトランス相互作用によってクラスターを形成します。 それらの細胞質ドメインは、選択的スプライシングにより、異なるアイソフォーム間で長さが異なります。たとえば、ヒトには 4 つのデスモグレイン アイソフォームと 3 つのデスモコリン アイソフォームが存在します。

デスモソームのアダプタータンパク質

デスモソームカドヘリンの細胞質ドメインは、プラコグロビンおよびプラコフィリンと呼ばれるアルマジロファミリーのタンパク質に結合し、高密度プラークを形成します。 これらのタンパク質は、デスモプラキンなどのさまざまなリンカータンパク質のドッキング部位として機能する特徴的なアームリピートを持っています。 デスモプラキンは、デスモソーム複合体に最も豊富に含まれるタンパク質です。 それらのカルボキシ末端にはプラキンリピートが含まれており、これが中間フィラメントに結合し、デスモソームプラークと細胞骨格の間に結合を形成します。

デスモソーム機能不全の疾患

デスモソーム機能不全は、通常、心臓や皮膚の障害として現れます。これらの組織は通常、高レベルの機械的歪みを受けています。 たとえば、デスモグレイン遺伝子の変異は、表皮肥厚や不整脈原性右室心筋症（ARVC）を引き起こす可能性があります。 さらに、デスモソームカドヘリンを標的とする自己抗体は、自己免疫疾患である尋常性天疱瘡を引き起こし、患者は弱い細胞間接着により表皮水疱を起こします。

デスモソームという用語は、ギリシャ語の「デスモ」と「癒着体」を意味する「ソーマ」に由来します。この構造が最初に観察されました...

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

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 glycoproteins have a large extracellular region with four cadherin repeats and one anchor domain that holds them in the cell membrane.

Desmogleins and desmocollins can pair as heterodimers. They form clusters through cis-interactions on the same cell and trans-interactions between adjacent cells. In humans, there are four desmoglein isoforms and three desmocollin isoforms, and their cytoplasmic domains can differ in length because of alternative splicing.

Inside the cell, the cadherins bind armadillo family proteins called plakoglobin and plakophilin. These proteins form a dense plaque. The plaque then recruits desmoplakin, the most abundant protein in a desmosomal complex. Desmoplakin uses its carboxy-terminal plakin repeats to bind intermediate filaments, which connects the desmosome to the cytoskeleton.

Problems with desmosomes often show up in the heart and skin, where cells face high mechanical strain. Mutations in desmoglein genes can cause epidermal thickening and arrhythmogenic right ventricular cardiomyopathy, or ARVC. Autoantibodies against desmosomal cadherins can also cause pemphigus vulgaris, an autoimmune disease that leads to epidermal blisters because cell-cell adhesion becomes weak.

Desmosomes and Cell Anchoring

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

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...

desmosomes

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 desmosomes hold cells together, link to intermediate filaments, and why defects can affect skin and heart tissue in humans.

Desmosomes and Cell Anchoring | 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。

Desmosomes and Cell Anchoring

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