Laminin and entactin and major components of basement membranes. It is well documented that laminin mediated cell adhesion and spreading, neurite outgrowth and neuronal survival. There is also evidence to suggest that it is involved in axonal guidance, formation of neuromuscular junctions, kidney development, embryogenesis and maintenance of differentiated functions. The interactions of laminin and its receptor has been implicated in the metastatic process and in the recognition of natural killer lymphocytes and their target cells. The involvement of entactin in the function of basement membranes is less clear. It found in tight non-covalent association with laminin and recent evidence suggests that it may also be involved in cell attachment. The objectives of this proposal are to (a) define the structures in laminin that are required for cell attachment. (b) isolate and characterize the cell surface molecules the mediate laminin binding, (c) clarify the role of entactin in basement membrane function especially with respect to cell attachment and (d) explore the regulation of expression of the laminin binding macromolecules. The primary sequences of laminin and entactin will be determined by recombinant DNA techniques. Fusion proteins containing segments of each molecule will be generated to be used as probes for cell binding and as antigens. Polyclonal and monoclonal antibodies produced with the fusion proteins and polypeptides derived from laminin and entactin will be employed to eluctidate their bindings domains. The long range objective of the project is to define the mechanisms whereby the extracellular matrix influences the behavior of cells during metastasis, embryogenesis and cellular differentiation.
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