Phosphorylation of synapsin I by cAMP-dependent protein kinase controls synaptic vesicle dynamics in developing neurons

Dario Bonanomi, Andrea Menegon, Annarita Miccio, Giuliana Ferrari, Anna Corradi, Hung Teh Kao, Fabio Benfenati, Flavia Valtorta

Research output: Contribution to journalArticlepeer-review

Abstract

In developing neurons, synaptic vesicles (SVs) undergo cycles of exo-endocytosis along isolated axons. However, it is currently unknown whether SV exocytosis is regulated before synaptogenesis. Here, we show that cAMP-dependent pathways affect SV distribution and recycling in the axonal growth cone and that these effects are mediated by the SV-associated phosphoprotein synapsin I. The presence of synapsin I on SVs is necessary for the correct localization of the vesicles in the central portion of the growth cone. Phosphorylation of synapsin I by cAMP-dependent protein kinase (protein kinase A) causes the dissociation of the protein from the SV membrane, allowing diffusion of the vesicles to the periphery of the growth cone and enhancing their rate of recycling. These results provide new clues as to the bases of the well known activity of synapsin I in synapse maturation and indicate that molecular mechanisms similar to those operating at mature nerve terminals are active in developing neurons to regulate the SV life cycle before synaptogenesis.

Original languageEnglish
Pages (from-to)7299-7308
Number of pages10
JournalJournal of Neuroscience
Volume25
Issue number32
DOIs
Publication statusPublished - Aug 10 2005

Keywords

  • Growth cone
  • Knock-out mice
  • Lentiviruses
  • Phosphorylation
  • Synapse formation
  • Trafficking

ASJC Scopus subject areas

  • Neuroscience(all)

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