Name: cadherins guide cell sorting in tissues
Uploaded: 2023-04-30T11:55:30.000Z
Duration: 1 min 19 s
Channel: JoVE

細胞接着分子の一種であるカドヘリンは、細胞間の選択的接着を媒介するため、組織構造の確立と維持に重要な役割を果たします。
未分化細胞は、発生過程で特定のカドヘリンを発現し、上皮細胞上のE-カドヘリンやニューロン上のN-カドヘリンなど、異なる組織タイプに分化します。
カドヘリンは一般に同じ種類の他のカドヘリンと結合するため、細胞は互いに選択的に接着することができます。
さらに、カドヘリンレベルが高い細胞は、カドヘリンレベルが低い細胞から分離します。
したがって、カドヘリンの量的および定性的特異性の両方が、細胞を組織に選別し、組織化するのに役立ちます。
逆に、カドヘリン発現のダウンレギュレーションは、細胞接着の喪失につながります。
例えば、カドヘリンの発現を停止した腫瘍細胞は、隣接する細胞から分離し、組織の制約を克服することができます。
上皮間葉転換(EMT)と呼ばれるこの移行は、腫瘍細胞から悪性細胞への進行における重要なステップです。

<ol>
	<li>「神経系の発達におけるカドヘリン発現の調節」 Cell adhesion & migration 8.1 (2014): 19-28.</li>
	<li>Berx, Geert, and Frans Van Roy. 「がんにおけるカドヘリンスーパーファミリーのメンバーの関与」 Cold Spring Harbor perspectives in biology 1.6 (2009): a003129.</li>
</ol>

c組織組織におけるカドヘリン

Cadherins in Tissue Organization

カドヘリンは、180 種類を超える変異体からなる細胞接着分子のスーパーファミリーで、特定の組織では特定のカドヘリン タイプの組み合わせが発現します。カドヘリンは一般に同種親和性結合を示します。つまり、1 つの細胞のカドヘリンは、別の細胞の同じまたは近縁のタイプのカドヘリンに結合します。したがって、同じタイプの細胞は、互いに結合してクラスターに分かれて組織を形成するという特定の親和性を持っています。

発達中の細胞選別

細胞選別は、両生類の胚を使った初期の実験で実証されているように、胚発生と発達の過程で重要な役割を果たします。若い胚の細胞を分離して混ぜ合わせます。この混合物を凝集させると、類似の細胞が集まって構造を形成します。これらの構造は、中胚葉、表皮、神経管などの胚層に似ています。カドヘリンの発現は、細胞が発達中に分化するにつれて変化し、脊椎動物の神経管のような複雑な構造の形成を可能にします。外胚葉層から神経溝が形成されると、神経板細胞はカドヘリンの発現を E カドヘリンから N カドヘリンに切り替えます。神経板境界の細胞もカドヘリン 6B などの他のカドヘリンの発現を開始し、2 つの端を一緒にして神経管の挟み込みを促進します。

カドヘリンと悪性腫瘍

カドヘリンを介した細胞間接着は、多細胞生物の組織シグナル伝達を維持する重要なメカニズムです。しかし、癌組織ではこの細胞接着が崩壊します。多くの上皮腫瘍細胞は、さまざまな転写調節因子の助けを借りて、E カドヘリン分子の発現を部分的または完全に停止します。たとえば、Twist と呼ばれる転写調節因子は E カドヘリンの発現を阻害し、腫瘍細胞が隣接する細胞に接着するのを防ぎます。この変化は上皮間葉転換 (EMT) と呼ばれます。これは悪性腫瘍への進行の特徴的な特徴であり、腫瘍細胞が他の組織から脱出して侵入することを可能にします。悪性乳がん細胞で Twist を実験的に阻害すると、悪性腫瘍が軽減されます。対照的に、正常な上皮細胞は Twist の発現を増加させることで EMT を誘発できます。

C組織組織におけるカドヘリン

カドヘリンは、180を超えるバリアントを含む細胞接着分子のスーパーファミリーであり、特定の組織は特定の組み合わせを発現します...

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 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 become tissues.

Cell sorting is important during embryogenesis and development. Early experiments with amphibian embryos showed this clearly. When young embryo cells were separated, mixed, and then allowed to come together again, similar cells clustered and formed structures like the mesoderm, epidermis, and neural tube.

Cadherin expression also changes as cells differentiate. During vertebrate neural tube formation, neural plate cells switch from E-cadherin to N-cadherin as the neural groove forms from the ectoderm. Cells at the neural plate border also begin expressing other cadherins, such as cadherin 6B. These changes help bring the two sides together and support pinching off of the neural tube.

Cadherin-mediated adhesion also helps maintain tissue homeostasis in multicellular organisms. In cancer, this adhesion can break down. Many epithelial tumor cells lose some or all E-cadherin expression, often with help from transcription regulators. One example is Twist, which blocks E-cadherin expression and reduces cell adhesion to neighboring cells.

Cadherins Guide Cell Sorting in Tissues

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 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, sort into tissues, shape the neural tube, and change during cancer-related EMT in high school biology.

Cadherins Guide Cell Sorting in Tissues | 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 Guide Cell Sorting in Tissues

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