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

Franco Onofri, Silvia Giovedì, Paola Vaccaro, Andrew J. Czernik, Flavia Valtorta, Pietro De Camilli, Paul Greengard, Fabio Benfenati

Research output: Contribution to journalArticlepeer-review

Abstract

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 now 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 synapsin 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 synapsin 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.

Original languageEnglish
Pages (from-to)12168-12173
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number22
DOIs
Publication statusPublished - Oct 28 1997

Keywords

  • SH3 domains
  • Synapses
  • Synaptic vesicles

ASJC Scopus subject areas

  • Genetics
  • General

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