title: Effects of phosphorylation and neuronal activity on the control of synapse formation by synapsin I.
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 siRNA-mediated 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 activity-dependent 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.
authors: San Raffaele Scientific Institute and Vita-Salute University, Via Olgettina 58, 20132 Milano,  Italy.
authors: Laura E
authors: LE
authors: Perlini
authors: Francesca
authors: F
authors: Botti
authors: Eugenio F
authors: EF
authors: Fornasiero
authors: Maila
authors: M
authors: Giannandrea
authors: Dario
authors: D
authors: Bonanomi
authors: Mario
authors: M
authors: Amendola
authors: Luigi
authors: L
authors: Naldini
authors: Fabio
authors: F
authors: Benfenati
authors: Flavia
authors: F
authors: Valtorta
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016704:Synapsins