Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity

Synapsin I is a synaptic vesicle-associated phosphoprotein that has been implicated in the formation of presynaptic specializations and in the regulation of neurotransmitter release, The nonreceptor tyrosine kinase c-Src is enriched on synaptic vesicles, where it accounts for most of the vesicle-associated tyrosine kinase activity, Using overlay, affinity chromatography, and coprecipitation assays, we have nom shown that synapsin I is the major binding protein for the Src homology 3 (SH3) domain of c-Src in highly purified synaptic vesicle preparations, The interaction was mediated by the proline-rich domain D of sgnapsin I and was not significantly affected by stoichiometric phosphorylation of synapsin I at any of the known regulatory sites, The interaction of purified c-Src and synapsin I resulted in a severalfold stimulation of tyrosine kinase activity and was antagonized by the purified c-Src-SH3 domain, Depletion of synapsin I from purified synaptic vesicles resulted in a decrease of endogenous tyrosine kinase activity, Portions of the total cellular pools of synapsin I and Src were coprecipitated from detergent extracts of rat brain synaptosomal fractions using antibodies to either protein species. The interaction between sgnapsin I and c-Src, as well as the synapsin I-induced stimulation of tyrosine kinase activity, may be physiologically important in signal transduction and in the modulation of the function of axon terminals, both during synaptogenesis and at mature synapses.