Name: cadherins in cell junctions and disease
Uploaded: 2023-04-30T11:54:59.000Z
Duration: 1 min 25 s
Channel: JoVE

カドヘリンは、カルシウム依存性細胞接着分子またはCAMのスーパーファミリーです。
すべてのカドヘリンは、小さなC末端細胞質ドメイン、単一の膜貫通ドメイン、および複数の細胞外カドヘリンまたはECドメインからなる基本構造を持っています。
これらのECドメインは、柔軟なヒンジ領域によって互いにリンクされており、それぞれに3つのカルシウム結合ポケットがあります。
カルシウムイオンが結合すると、カドヘリンは硬くなり、他のカドヘリンへのシス結合およびトランス結合が可能になります。
シス結合では、同じ細胞上のカドヘリンが互いに結合してクラスターを形成する一方で、隣接する細胞上のカドヘリンのECドメインの相互作用により、トランス結合が起こります。
EC1と呼ばれる膜から最も遠いN末端のECドメインは、ノブとポケットの構造をしています。トランスバインディング中、1つのEC1のつまみは、隣接するセル上の別のEC1のポケットに収まります。
これにより、1つのタイプのカドヘリンは、同じタイプのカドヘリンを優先的に結合し、ホモフィリック結合を行います。
1対のカドヘリン間の相互作用は比較的弱いですが、カドヘリンクラスターは集合的に強いトランス結合を形成することができます。このような複合体は、アンカーセル結合を形成します。

<ol>
	<li>「カドヘリンとカテニンの構造と生化学」 生物学におけるコールドスプリングハーバーの展望 1.3 (2009): a003053.</li>
</ol>

カドヘリンの構造

Structure of Cadherins

カドヘリンは、最初に発見された細胞接着分子の 1 つです。 「カドヘリン」という用語は、そのカルシウム依存性の付着特性に基づいています。 上皮細胞、神経細胞、胎盤細胞で発見された最初のカドヘリンは、それぞれ E-カドヘリン、P-カドヘリン、N-カドヘリンと名付けられました。 これらの古典的なカドヘリンは配列と構造の類似性を共有しています。 細胞シグナル伝達に関与するものを含む他のカドヘリンは、非古典的カドヘリンに分類されます。 このカドヘリンの多様性は、ゲノム内の複数のカドヘリン遺伝子と転写時の選択的 RNA スプライシングから生じます。

細胞接合部のカドヘリン

カドヘリンは、複数の細胞外結合ドメインを持つ膜貫通タンパク質です。 それらの細胞質ドメインは、細胞骨格に接続するリンカータンパク質に結合します。 カドヘリンはシス結合によって原形質膜上に集まり、細胞結合と呼ばれる大きな複数のタンパク質複合体を形成します。 E-カドヘリンなどの古典的カドヘリンが接着結合を形成するのに対し、デスモグレインやデスモコリンなどの非古典的カドヘリンはデスモソーム結合を形成します。 これらの細胞接合は、細胞を保持し、上皮などの組織に機械的強度を提供する機能を果たします。

カドヘリンの臨床的意義

カドヘリンは、細胞接着、組織形成、および細胞間コミュニケーションにおいて重要な役割を果たします。 その結果、それらの構造、発現、安定性におけるあらゆる変化が臨床症状として現れる可能性があります。 細胞が隣接する細胞との接触を失うと、細胞は組織から離れて他の組織に侵入する可能性があります。 カドヘリン遺伝子の変異による細胞接着の喪失は、乳房悪性細胞で見られるような腫瘍の悪性化に関連しています。 病原体はまた、宿主細胞に付着して侵入するための受容体としてカドヘリンを使用します。 たとえば、カドヘリン CDHR3 は肺上皮で高度に発現しており、風邪の原因となるクラス C ライノウイルス (RV-C) によって受容体として使用されます。

カドヘリンは、最初に発見された細胞接着分子の1つでした。「カドヘリン」という用語は、カルシウム依存性に基づいています...

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

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 in the genome and from alternative RNA splicing during transcription.

Cadherins are transmembrane proteins. They have several extracellular binding domains and a cytosolic domain inside the cell. The cytosolic region binds linker proteins, which connect cadherins to the cytoskeleton. Cadherins also cluster on the plasma membrane through cis-binding, which helps form large protein complexes called cell junctions.

Classical cadherins such as E-cadherin form adherens junctions. Non-classical cadherins such as desmoglein and desmocollin form desmosomal junctions. These junctions hold cells together and give mechanical strength to tissues such as epithelium.

Cadherins are important for cell adhesion, tissue formation, and communication between cells. Changes in their structure, expression, or stability can lead to disease. When cells lose contact with neighboring cells, they may break free from the tissue and invade other tissues. Mutations in cadherin genes are linked to tumor malignancy, including in breast cancer cells. Some pathogens also use cadherins as receptors to attach to and enter host cells. One example is CDHR3, which is highly expressed in lung epithelium and is used by class-C rhinovirus, or RV-C, the virus that causes the common cold.

Cadherins in Cell Junctions and Disease

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 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 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 cadherins help cells stick together, form junctions, and support tissues, and how changes in cadherins can contribute to cancer and infection.

Cadherins in Cell Junctions and Disease | 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。

Cadherins in Cell Junctions and Disease

Description

Transcript

Tags