Neurons interact with several different extracellular matrix glycoproteins, as well as with adhesion molecules on the surfaces of other cells. These help regulate neuroblast proliferation, neuronal determination, cell migration, axon growth, synapse formation, and other aspects of neuronal differentiation. A family of receptor heterodimers for extracellular matrix and cell surface glycoproteins, named integrins, has been identified as major mediators of neuronal interactions with extracellular matrix glycoproteins - vitronectin, thrombospondin, and tenascin have been shown to interact with neurons. The latter two proteins have been shown to regulate aspects of neuronal differentiation in vivo. Work in this laboratory has partially characterized integrins that mediate neuronal interactions with nitronectin and thrombospondin. This work has also identified one novel integrin with primary expression in neurons and has provided evidence that subsets of neurons express integrins not identified and characterized at present. In this grant, work will attempt to characterize the integrin receptors used by neurons to interact with nitronectin and thrombospondin. Experiments will determine whether integrins also mediate some of the interactions of neurons with tenascin and, if so, will attempt to identify and characterize those receptors. Work will continue on determining the expression pattern, ligand-binding specificities, and functions of the novel, primarily neural integrin subunit, named alpha8, recently identified in this laboratory. Efforts will be made to prepare specific antibodies to and characterize the novel integrins that appear to be expressed on sensory neurons and retinal neurons.
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