ASSOCIATION OF BETA-1 INTEGRIN WITH PHOSPHOTYROSINE IN GROWTH CONE FILOPODIA

Filopodia of growth cones are key elements in the transduction of extr acellular cues that guide axon growth during development. How they are specialized to carry out this role is poorly understood. We previousl y had found tyrosine phosphorylated protein to be heavily concentrated at the tips of many filopodia of Aplysia growth cones in certain cult uring conditions, suggesting that tyrosine phosphorylation might be in volved in filopodial specialization. Immunocytochemistry was used to a nalyze the protein composition of the tip aggregates to determine whet her there was an association of the tip phosphorylation with any impor tant extracellular cue, beta 1 integrin, a subunit of the receptor for laminin-type neurite growth promoters, coconcentrated with phosphotyr osine at filopodial tips of both Aplysia and mouse growth cones. Sever al observations indicated that the association of beta 1 integrin with phosphotyrosine is close, beta 1 integrin and phosphotyrosine are kno wn to colocalize at focal contacts, sites of adhesion of cells to the extracellular matrix, but the composition and behavior of the tip aggr egates mark them as distinct structures. Also found in the tip aggrega tes was a member of the ezrin-radizin-moesin family of proteins, which are thought to link membrane proteins to submembranous bundles of act in filaments. Use of an inhibitor of protein-tyrosine kinases to deple te tip phosphotyrosine also caused disappearance of beta 1 integrin fr om the tip, suggesting a role for tyrosine phosphorylation in facilita ting interaction of growth cones with certain environmental cues by fo stering the aggregation of receptors in filopodia.