Association of beta 1 integrin with phosphotyrosine in growth cone filopodia.
Filopodia of growth cones are key elements in the transduction of extracellular cues that guide axon growth during development. How they are specialized to carry out this role is poorly understood. We previously had found tyrosine phosphorylated protein to be heavily concentrated at the tips of many filopodia of Aplysia growth cones in certain culturing conditions, suggesting that tyrosine phosphorylation might be involved in filopodial specialization. Immunocytochemistry was used to analyze the protein composition of the tip aggregates to determine whether there was an association of the tip phosphorylation with any important extracellular cue. beta 1 integrin, a subunit of the receptor for laminin-type neurite growth promoters, coconcentrated with phosphotyrosine at filopodial tips of both Aplysia and mouse growth cones. Several observations indicated that the association of beta 1 integrin with phosphotyrosine is close. beta 1 integrin and phosphotyrosine are known to colocalize at focal contacts, sites of adhesion of cells to the extracellular matrix, but the composition and behavior of the tip aggregates mark them as distinct structures. Also found in the tip aggregates was a member of the ezrin-radixin-moesin family of proteins, which are thought to link membrane proteins to submembranous bundles of actin filaments. Use of an inhibitor of protein-tyrosine kinases to deplete tip phosphotyrosine also caused disappearance of beta 1 integrin from the tip, suggesting a role for tyrosine phosphorylation in facilitating interaction of growth cones with certain environmental cues by fostering the aggregation of receptors in filopodia.
Wu
D Y
DY
Department of Pharmacology, Columbia University, New York, New York 10032, USA.
Wang
L C
LC
Mason
C A
CA
Goldberg
D J
DJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001048:Aplysia; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D007150:Immunohistochemistry; D016023:Integrins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019000:Phosphotyrosine / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016023:Integrins; D019000:Phosphotyrosine