纤连蛋白通过 ECM 连接细胞

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.

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.

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.

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.

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.

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.

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.