ATP binding to Synaspsin IIa regulates usage and clustering of vesicles in terminals of hippocampal neurons

Yoav Shulman, Alexandra Stavsky, Tatiana Fedorova, Dan Mikulincer, Merav Atias, Igal Radinsky, Joy Kahn, Inna Slutsky, Daniel Gitler

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Synaptic transmission is expensive in terms of its energy demands and was recently shown to decrease the ATP concentration within presynaptic terminals transiently, an observation that we confirm.Wehypothesized that, in addition to being an energy source, ATP may modulate the synapsins directly. Synapsins are abundant neuronal proteins that associate with the surface of synaptic vesicles and possess a well defined ATP-binding site of undetermined function. To examine our hypothesis, we produced a mutation (K270Q) in synapsin IIa that prevents ATP binding and reintroduced the mutant into cultured mouse hippocampal neurons devoid of all synapsins. Remarkably, staining for synaptic vesicle markers was enhanced in these neurons compared with neurons expressing wild-type synapsin IIa, suggesting overly efficient clustering of vesicles. In contrast, the mutation completely disrupted the capability of synapsin IIa to slow synaptic depression during sustained 10 Hz stimulation, indicating that it interfered with synapsin-dependent vesicle recruitment. Finally, we found that the K270Q mutation attenuated the phosphorylation of synapsin IIa on a distant PKA/CaMKI consensus site known to be essential for vesicle recruitment. We conclude that ATP binding to synapsin IIa plays a key role in modulating its function and in defining its contribution to hippocampal short-term synaptic plasticity.

Original languageEnglish
Pages (from-to)985-998
Number of pages14
JournalJournal of Neuroscience
Issue number3
StatePublished - 21 Jan 2015


  • ATP
  • Phosphorylation
  • Short-term plasticity
  • Synapsin
  • Synaptic vesicle
  • Vesicle pools

ASJC Scopus subject areas

  • Medicine (all)


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