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

钙黏蛋白是一类细胞黏附分子，介导细胞之间的选择性黏附，因此在组织结构的建立和维持中发挥着关键作用。
在发育过程中，未分化的细胞在分化为不同类型的组织时，会在其表面表达特定的钙黏蛋白，例如上皮细胞上的E-钙黏蛋白和神经元上的N-钙黏蛋白。
由于钙黏蛋白通常与同类型的其他钙黏蛋白结合，细胞能够选择性地相互黏附。
此外，表达较高钙黏蛋白水平的细胞会与表达较低水平的细胞分离。
因此，钙黏蛋白的定量和定性特异性共同帮助将细胞分选并组织成组织。
相反，钙黏蛋白表达的下调会导致细胞黏附的丧失。
例如，停止表达钙黏蛋白的肿瘤细胞可从邻近细胞上脱离，并突破组织的限制。
这种转变被称为上皮-间质转化（epithelial to mesenchymal transition，EMT），是肿瘤细胞向恶性细胞进展的关键步骤。

<ol>
	<li>Paulson， Alicia F.， et al. "神经系统发育中钙粘蛋白表达的调节。" 细胞粘附与迁移 8.1 （2014）:19-28。</li>
	<li>Berx、Geert 和 Frans Van Roy。"钙粘蛋白超家族成员参与癌症。"冷泉港生物学观点 1.6 （2009）:a003129。</li>
</ol>

钙粘蛋白在组织形成中的作用

Cadherins in Tissue Organization

钙粘蛋白是细胞粘附分子的超家族，包含 180 多种变体，特定组织表达特定组合的钙粘蛋白类型。钙粘蛋白通常表现出同源结合； 即，一个细胞上的钙粘蛋白与另一细胞上相同或密切相关类型的钙粘蛋白结合。因此，相同类型的细胞具有特定的亲和力，可以相互结合并将自身分类成簇以形成组织。

发育过程中的细胞分选

细胞分类在胚胎发生和发育过程中起着至关重要的作用，这在早期对两栖动物胚胎的实验中得到了证明。来自年轻胚胎的细胞被分离并混合。当这种混合物聚集时，相似的细胞聚集在一起，形成结构。这些结构类似于胚胎层，如中胚层、表皮和神经管。钙粘蛋白的表达随着细胞在发育过程中的分化而变化，从而形成复杂结构，例如脊椎动物的神经管。当神经沟从外胚层形成时，神经板细胞将其钙粘蛋白表达从 E-钙粘蛋白转变为 N-钙粘蛋白。神经板边缘的细胞也开始表达其他钙粘蛋白，如钙粘蛋白 6B，从而将两端连接在一起，并促进神经管的闭合。

钙粘蛋白与恶性肿瘤

钙粘蛋白介导的细胞间粘附是维持多细胞生物组织稳态的重要机制。然而，在癌组织中，这种细胞粘附会被破坏。许多上皮肿瘤细胞在各种转录调节因子的帮助下部分或完全停止表达 E-钙粘蛋白分子。例如，一种名为 Twist 的转录调节因子可抑制 E-钙粘蛋白的表达，从而防止肿瘤细胞粘附到邻近细胞。这种转变称为上皮间质转化（EMT）。这是恶性肿瘤进展的一个特征，使肿瘤细胞能够逃逸并侵入其他组织。通过实验阻断恶性乳腺癌细胞中的 Twist 可降低其恶性程度。相反，通过增加 Twist 表达，可以诱导正常上皮细胞发生 EMT。

钙黏蛋白是一类细胞黏附分子的超家族，包含超过180种亚型，特定组织表达其中特定的组合……

Education

教育

JoVE Core

Cell Biology

细胞生物学

Unit 1

第一单元

Cell-Cell Interactions

细胞间相互作用

KEY TERMS AND CONCEPTS

关键术语与概念

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 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.

Cadherins Guide Cell Sorting in Tissues

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