Effects of phosphorylation and neuronal activity on the control of synapse formation by synapsin I

Laura E. Perlini, Francesca Botti, Eugenio F. Fornasiero, Maila Giannandrea, Dario Bonanomi, Mario Amendola, Luigi Naldini, Fabio Benfenati, Flavia Valtorta

Research output: Contribution to journalArticlepeer-review

Abstract

Synapsins are synaptic vesicle (SV)-associated proteins that regulate synaptic transmission and neuronal differentiation. At early stages, Syn I and II phosphorylation at Ser9 by cAMP-dependent protein kinase (PKA) and Ca 2+/calmodulin-dependent protein kinase I/IV modulates axon elongation and SV-precursor dynamics. We evaluated the requirement of Syn I for synapse formation by siRNAmediated knockdown as well as by overexpression of either its wild-type (WT) form or its phosphorylation mutants. Syn1 knockdown at 14 days in vitro caused a decrease in the number of synapses, accompanied by a reduction of SV recycling. Although overexpression of WT Syn I was ineffective, overexpression of its phosphorylation mutants resulted in a complex temporal regulation of synapse density. At early stages of synaptogenesis, phosphomimetic Syn I S9E significantly increased the number of synapses. Conversely, dephosphomimetic Syn I S9A decreased synapse number at more advanced stages. Overexpression of either WT Syn I or its phosphomimetic S9E mutant rescued the decrease in synapse number caused by chronic treatment with tetrodotoxin at early stages, suggesting that Syn I participates in an alternative PKA-dependent mechanism that can compensate for the impairment of the activitydependent synaptogenic pathway. Altogether these results indicate that Syn I is an important regulator of synapse formation, which adjusts synapse number in response to extracellular signals.

Original languageEnglish
Pages (from-to)3643-3653
Number of pages11
JournalJournal of Cell Science
Volume124
Issue number21
DOIs
Publication statusPublished - Nov 1 2011

Keywords

  • Camp-dependent protein kinase (PKA)
  • Hippocampal neuron
  • Lentiviral vector
  • Synaptic vesicle
  • Tetrodotoxin (TTX)

ASJC Scopus subject areas

  • Cell Biology

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