MOLECULAR MECHANISMS OF CELL SUBSTRATE INTERACTIONS

纤维连接蛋白与其整合素受体的相互作用起着重要作用

Interactions of fibronectin with its integrin receptors play important roles in embryonic development, wound healing and the progression of diseases such as cancer. Approaches involving monoclonal antibodies, molecular and cell biology, and physical chemistry are being employed to elucidate molecular mechanisms underlying the interactions of fibronectin with integrins with the goal of understanding the roles of these glycoproteins in complex biological processes in order to develop bioadhesive substrates and to provide the bases for rational medical intervention in diseases involving abnormal cellular adhesion and migration Besides the RGD and the synergistic regions on fibronectin, a third site to the amino-terminal side of the synergistic region has been identified that is required for assembly of fibronectin matrices in vivo, though not for binding of fibronectin to integrins. Fibronectin- integrin interactions are not required for fibroblast-mediated collagen gel contraction nor for odontoblast differentiation, although such interactions play a role in the adhesion of these cells. Up-regulation of keratinocyte migration during wound healing depends on the redistribution of integrins, expression of the alpha5beta1 fibronectin receptor integrin, and the acquisition of a migratory phenotype. Studies currently underway will examine the three-dimensional structure of the fibronectin cell-adhesive region in solution, and the role of integrins in transmembrane signal transduction.