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

Synapsins constitute a family of synaptic vesicle proteins essential for re gulating neurotransmitter release. Only two domains are conserved in all sy napsins: 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 synap sin phosphorylation in the A domain, at the only phosphorylation site share d by all synapsins, dissociates synapsins from synaptic vesicles. Furthermo re, we show that the A domain binds phospholipids and is inhibited by phosp horylation. Our results suggest a novel mechanism by which proteins reversi bly bind to membranes using a phosphorylation-dependent phospholipid-bindin g domain. The dynamic association of synapsins with synaptic vesicles corre lates with their role in activity-dependent plasticity.