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纤连蛋白通过 ECM 连接细胞
纤连蛋白是一种存在于胚胎和成体组织的细胞外基质中的粘附糖蛋白。这些分子主要有助于调节细胞运动和附着。纤连蛋白分子由两条相同的多肽链组成，它们通过 C 端的一对二硫键相互连接。
蛋白聚糖和胶原蛋白都附着在纤连蛋白上，而纤连蛋白又附着在整合素蛋白上。这些整合素蛋白与缺乏细胞壁的真核细胞质膜中的跨膜蛋白相…
纤连蛋白是存在于细胞外基质中的黏附性糖蛋白，其主要功能是将细胞与基质连接在一起。
纤维连接蛋白由两个大亚基组成，这两个亚基在其C端通过几对二硫键连接，形成二聚体。两个亚基均含有多种重复结构域，可与胶原原纤维、蛋白聚糖中的肝素以及整合素（即细胞黏附受体）结合。通过这种方式，纤维连接蛋白将细胞与基质成分连接起来。
整合素的结合受精氨酸、甘氨酸和天冬氨酸残基（即RGD重复序列）存在的显著影响，这在纤维连接蛋白的主要重复结构域之一——III型结构域中可见。
一旦与纤连蛋白结合，整合素便可与肌动蛋白丝结合，在细胞外成分与细胞骨架之间形成桥梁。这种结合会传递张力，使纤连蛋白被拉伸，暴露出其隐蔽的结合位点，从而允许多个纤连蛋白二聚体进一步结合，形成纤连蛋白原纤维。
这些纤维连接蛋白纤维有助于表皮细胞的迁移和增殖，促进伤口愈合等多种生物学过程。
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Q1: What is the basic structure of a fibronectin molecule?
Fibronectin consists of two identical polypeptide subunits joined at their C-terminal by disulfide bonds, forming a dimer. Both subunits contain repeating domains that bind to various extracellular components including collagen fibrils, heparin, proteoglycans, and integrins. This dimeric structure enables fibronectin to bridge cells with the extracellular matrix.
Q2: How do fibronectins connect cells to the extracellular matrix?
Fibronectins bind to integrins, cell-adhesion receptors on the cell surface, through RGD repeats in their type III domains. Once bound to fibronectin, integrins connect to actin filaments in the cytoskeleton. This creates a bridge linking extracellular matrix components with the cell's internal structure, enabling cell attachment and communication with the matrix.
Q3: What role do RGD repeats play in fibronectin binding?
RGD repeats, composed of arginine, glycine, and aspartate residues, are found in fibronectin's type III domains and greatly influence integrin binding. These sequences are critical recognition sites that allow integrins to bind fibronectin with high specificity. RGD-mediated binding initiates the cascade that connects cells to matrix components and facilitates cellular responses.
Q4: How do fibronectin fibrils form in the extracellular matrix?
When integrins bind fibronectin, tension is transmitted through the molecule, stretching it and exposing cryptic binding sites. Multiple fibronectin dimers then bind to these exposed sites, forming fibronectin fibrils. These fibrils support epidermal cell migration and proliferation, facilitating biological processes like wound healing and tissue remodeling.
Q5: What are the two types of fibronectin found in vertebrates?
Vertebrates have soluble plasma fibronectin, produced by hepatocytes and found in blood plasma, and insoluble cellular fibronectin, located in the extracellular matrix. Plasma fibronectin plays a role in blood clotting by depositing at injury sites alongside fibrin. Fibroblasts produce the insoluble cellular fibronectin that forms the extracellular matrix structure.
Q6: What happens to plasma fibronectin after it is deposited at an injury site?
Plasma fibronectin is deposited along with fibrin at injury sites to help stop bleeding. After clotting occurs, proteases secreted by fibroblasts digest the plasma fibronectin. Meanwhile, fibroblasts produce insoluble cellular fibronectin that forms the extracellular matrix, replacing the temporary clot with permanent tissue structure.
Q7: How do fibronectins interact with collagen and proteoglycans in the matrix?
Fibronectin's repeating domains bind directly to collagen fibrils and heparin of proteoglycans, anchoring these major extracellular matrix components. By simultaneously binding integrins on cells and collagen and proteoglycans in the matrix, fibronectins act as molecular bridges. This multi-binding capability makes fibronectins essential adhesive glycoproteins that organize and stabilize the extracellular matrix structure.