title: A phospho-switch controls the dynamic association of synapsins with synaptic vesicles.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical School, Dallas 75235, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hosaka
authors.forename: R E
authors.initials: RE
authors.lastname: Hammer
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D013379:Substrate Specificity; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D016704:Synapsins; D017868:Cyclic AMP-Dependent Protein Kinases