A phospho-switch controls the dynamic association of synapsins with synaptic vesicles

Neuron. 1999 Oct;24(2):377-87. doi: 10.1016/s0896-6273(00)80851-x.


Synapsins constitute a family of synaptic vesicle proteins essential for regulating neurotransmitter release. Only two domains are conserved in all synapsins: a short N-terminal A domain with a single phosphorylation site for cAMP-dependent protein kinase (PKA) and CaM Kinase I, and a large central C domain that binds ATP and may be enzymatic. We now demonstrate that synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles. Furthermore, we show that the A domain binds phospholipids and is inhibited by phosphorylation. Our results suggest a novel mechanism by which proteins reversibly bind to membranes using a phosphorylation-dependent phospholipid-binding domain. The dynamic association of synapsins with synaptic vesicles correlates with their role in activity-dependent plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Activation / physiology
  • Exocytosis / physiology
  • Mice
  • Molecular Sequence Data
  • Phospholipids / metabolism
  • Phosphorylation
  • Rats
  • Substrate Specificity
  • Synapsins / genetics
  • Synapsins / metabolism*
  • Synaptic Vesicles / metabolism*


  • Phospholipids
  • Synapsins
  • Cyclic AMP-Dependent Protein Kinases