The extracellular matrix plays a vital role in the normal function of complex organisms. It is implicated in organogenesis, cell differentiation, metastasis, neuronal guidance, wound healing and protective functions. A specialized sheet-like structure of the extracellular matrix, the basal lamina, underlies various tissues and is in intimate contact with the plasma membrane of the overlying cells. The major components of this structure are laminin, type IV collagen, heparan sulfate proteoglycan and entactin. The molecular structures of these molecules have been largely determined by recombinant DNA approaches and the biological activity of each molecule is being elucidated. Transmembrane receptors have been identified and characterized for laminin and type IV collagen. These transmembrane receptors are believed to be responsible for transmitting information from the extracellular to the intracellular compartment and thereby eliciting specific cellular responses. The biological properties of entactin which include promotion of cell attachment, chemotaxis, phagocytosis and neutrophil degranulation are only now being uncovered. Furthermore , entactin appears to be important in organizing the extracellular matrix through its interactions with laminin, type IV collagen and fibronectin. It is the purpose of this project to extend the studies on entactin and to correlate in vitro observations with in vivo biological functions. The experiments to be performed include (a) mapping the functional domains (b) isolation and characterization of transmembrane and other receptors (c) analysis of its role in the morphogenesis and development of the eye and (d) exploring its function in hemostasis and wound healing. A combination of immunological, biochemical and genetic approaches will be used to solve these problems. It is hoped that the results obtained will contribute to our understanding of basal lamina function at the molecular level in normal development and in pathological conditions.
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