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

桥粒是一种锚定连接，在承受机械应力的组织中更为丰富，例如心肌和肠上皮。
桥粒处的细胞黏附由桥粒钙黏蛋白介导，主要包括桥粒胶蛋白和桥粒芯糖蛋白，它们通过胞外结构域的异嗜性相互作用实现黏附。
钙黏蛋白的胞质区结合称为连环蛋白（plakoglobins）和斑珠蛋白（plakophilins）的连环蛋白家族成员，这些蛋白在胞质侧形成致密的斑块结构。
连环蛋白不能直接结合中间丝，而是通过桥粒斑蛋白（desmoplakin）与之连接——桥粒斑蛋白是一种属于斑蛋白家族的细胞骨架连接蛋白。
桥粒斑蛋白的N端结构域结合连环蛋白，其C端的斑蛋白重复序列结合中间丝。
因此，桥粒将相邻细胞的中间丝锚定在一起，在组织中形成跨细胞的细胞骨架网络。

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	<li>Delva、Emmanuella、Dana K. Tucker 和 Andrew P. Kowalczyk。"桥粒。"冷泉港生物学观点 1.2 （2009）:a002543。</li>
	<li>Garrod、David 和 Martyn Chidgey。"桥粒结构、组成和功能。"Biochimica et Biophysica Acta （BBA）-生物膜 1778.3 （2008）:572-587。</li>
	<li>Nekrasova、Oxana 和 Kathleen J. Green。"桥粒组装和动力学。"细胞生物学趋势 23.11 （2013）:537-546。</li>
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桥粒

Desmosomes

桥粒一词源自希腊语“desmo”和“soma”，意思是“粘附体”。这种结构在 1800 年代末首次被观察到，被描述为表皮中小而致密的结节。桥粒是纽扣状结构，有助于形成跨细胞的中间纤维互连网络。这些连接对于在机械应力下将细胞紧密连接并保持组织完整性至关重要。桥粒是包含桥粒钙粘蛋白的多蛋白复合物，桥粒钙粘蛋白通过各种衔接蛋白与中间纤维连接。

桥粒钙粘蛋白

钙粘蛋白形成桥粒的细胞外核心区域，并与相邻细胞上的钙粘蛋白结合。桥粒中有两种类型的钙粘蛋白——桥粒胶蛋白和桥粒芯胶蛋白。这些跨膜糖蛋白具有较大的细胞外部分，包含四个钙粘蛋白重复序列和一个将这些蛋白质锚定到细胞膜上的细胞外锚定结构域。桥粒胶蛋白和桥粒芯胶蛋白的异二聚体通过对同一细胞上的顺式相互作用，和相邻细胞之间的反式相互作用形成簇。由于选择性剪接，不同异构体的细胞质结构域的长度可能有所不同，例如，在人类中发现了四种桥粒胶蛋白异构体和三种桥粒芯胶蛋白异构体。

桥粒中的衔接蛋白

桥粒钙粘蛋白的细胞质结构域与称为斑球蛋白和斑亲蛋白的犰狳蛋白家族结合，形成致密斑块。这些蛋白质具有特征性的臂重复序列，可作为不同连接蛋白（例如桥粒斑蛋白）的对接位点。桥粒斑蛋白是桥粒复合物中最丰富的蛋白质。它们的羧基末端含有斑块重复序列，与中间丝结合，从而在桥粒斑块和细胞骨架之间形成连接。

桥粒功能障碍疾病

桥粒功能障碍通常表现为心脏和皮肤疾病——这些组织通常承受高水平的机械应变。例如，桥粒胶蛋白基因的突变可导致表皮增厚和致心律失常性右心室心肌病（ARVC）。此外，针对桥粒钙粘蛋白的自身抗体会导致自身免疫性疾病寻常型天疱疮，患者由于细胞间粘附力较弱而出现表皮水疱。

桥粒一词源自希腊语“desmo”和“soma”，意为“黏着体”。这一结构最初被观察到……

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

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 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.

Desmosomes and Cell Anchoring

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