Neurons have been shown to interact with several different extracellular matrix glycoproteins, each of which is likely to help regulate axon growth and guidance during development and nerve regeneration. A family of extracellular matrix heterodimer receptors, named integrins, has been partially characterized and shown to be major mediators of neuronal interactions with the extracellular matrix. The characterization of two neuronal integrin receptors that mediate binding to laminin and collagen IV will be completed. Their structures, properties and function will be studied using the purified receptor heterodimers and subunit-specific antibodies, and by isolating and analyzing the sequences of cDNA clones. Using antibodies and cDNAs, the distributions of these receptor subunits in the nervous system will be analyzed. We will try to understand how they are regulated during development and nerve regeneration. Efforts will be made to identify factors that regulate their expression and activity. Using subunit-specific antibodies, we will try to identify some of the functions of these receptors in development and regeneration. Possible effects of NGF, a model trophic factor, on the expression, localization and function of these receptors will be examined with assays of subunit mRNA, protein, surface protein, phosphorylation and cytoskeletal associations. Using molecular biological analyses, we will attempt to identify and characterize domains of the receptor subunits required for NGF-dependent and NGF-independent neuronal process outgrowth.
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