Synapsins contribute to the dynamic spatial organization of synaptic vesicles in an activity-dependent manner

Eugenio F. Fornasiero, Andrea Raimondi, Fabrizia C. Guarnieri, Marta Orlando, Riccardo Fesce, Fabio Benfenati, Flavia Valtorta

Research output: Contribution to journalArticle

Abstract

The precise subcellular organization of synaptic vesicles (SVs) at presynaptic sites allows for rapid and spatially restricted exocytotic release of neurotransmitter. The synapsins (Syns) are a family of presynaptic proteins that control the availability of SVs for exocytosis by reversibly tethering them to each other and to the actin cytoskeleton in a phosphorylation-dependent manner. Syn ablation leads to reduction in the density of SVproteins in nerve terminals and increased synaptic fatigue under high-frequency stimulation, accompanied by the development of an epileptic phenotype. We analyzed cultured neurons from wild-type and Syn I,II,III triple knock-out (TKO) mice and found that SVs were severely dispersed in the absence of Syns. Vesicle dispersion did not affect the readily releasable pool of SVs, whereas the total number of SVs was considerably reduced at synapses of TKO mice. Interestingly, dispersion apparently involved exocytosis-competent SVs as well; it was not affected by stimulation but was reversed by chronic neuronal activity blockade. Altogether, these findings indicate that Syns are essential to maintain the dynamic structural organization of synapses and the size of the reserve pool of SVs during intense SV recycling, whereas an additional Syn-independent mechanism, whose molecular substrate remains to be clarified, targets SVs to synaptic boutons at rest and might be outpaced by activity.

Original languageEnglish
Pages (from-to)12214-12227
Number of pages14
JournalJournal of Neuroscience
Volume32
Issue number35
DOIs
Publication statusPublished - Aug 29 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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