18 Integrins Mediate Interactions of Chick Sensory

Integrins are major receptors used by cells to interact with extracellular matrices. In this paper, we identify the first ligands for the f38 family of integrins, presenting evidence that integrin heterodimers containing the f83 subunit mediate interactions of chick sensory neurons with laminin-1, collagen IV, and fibronectin. A polyclonal antibody, anti-f38-Ex, was prepared to a bacterial fusion protein expressing an extracellular portion of the chicken 18 subunit. In nonreducing conditions, this antibody immunoprecipitated from surface-labeled embryonic dorsal root ganglia neurons a Mr 100 k protein, the expected Mr of the f38 subunit, and putative a subunit(s) of Mr 120 k. Affinity-purified anti-038-Ex strongly inhibited sensory neurite outgrowth on laminin-1, collagen IV, and fibronectin-coated substrata. Binding sites were identified in a heat-resistant domain in laminin-1 and in the carboxyl terminal, 40-kDa fibronectin fragment. On substrates coated with the carboxyl terminal fragment of fibronectin, antibodies to,1 and 188 were only partially effective alone, but were completely effective in combination, at inhibiting neurite out-growth. Results thus indicate that the integrin f83 subunit in association with one or more a subunits forms an important set of extracellular matrix receptors on sensory neurons