IDENTIFICATION OF INTEGRIN ALPHA(3)BETA-1 AS A NEURONAL THROMBOSPONDIN RECEPTOR MEDIATING NEURITE OUTGROWTH

Thrombospondins are a family of extracellular matrix proteins expresse d throughout the developing nervous system that promote neurite outgro wth in vitro and help mediate the migration of granule cells across th e molecular layer in explants of neonatal cerebellum. The receptors me diating these interactions have not previously been identified. In thi s study, monoclonal antibodies raised to the integrin alpha(3) beta(1) heterodimer are shown to inhibit neurite outgrowth by rat sympathetic neurons on thrombospondin-1. alpha(3) beta(1) is found to be expresse d on the cell body, neurites, and growth cones of sympathetic neurons in vitro and on sympathetic axons passing through the thrombospondin-r ich outer sheath of the superior cervical ganglion in vivo, consistent with its role in mediating axon outgrowth. A receptor-ligand binding assay is used to demonstrate the direct binding of immunopurified alph a(3) beta(1) to thrombospondin-1. These results demonstrate a direct i nteraction between the integrin alpha(3) beta(1) and thrombospondin-1, which mediates neurite outgrowth in vitro and is likely to mediate th e same interactions in vivo.