Integrins are major receptors used by cells to interact with extracellular matrices. In this paper, we identify the first ligands for the beta(8) family of integrins, presenting evidence that integrin heterodimers containing the beta(8) subunit mediate interactions of chick sensory neurons with laminin-1, collagen IV, and fibronectin. A polyclonal antibody, anti-beta(8)-Ex, was prepared to a bacterial fusion protein expressing an extracellular portion of the chicken beta(8) subunit. In nonreducing conditions, this antibody immunoprecipitated from surface-labeled embryonic dorsal root ganglia neurons a M(r) 100 k protein, the expected M(r) of the beta(8) subunit, and putative alpha subunit(s) of M(r) 120 k. Affinity-purified anti-beta(8)-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 beta(1) and beta(8) were only partially effective alone, but were completely effective in combination, at inhibiting neurite outgrowth. Results thus indicate that the integrin beta(8) subunit in association with one or more ct subunits forms an important set of extracellular matrix receptors on sensory neurons.
