title: Phosphorylation of synaptic vesicle protein 2 modulates binding to synaptotagmin.
abstract: Synaptic vesicle protein 2 (SV2) is a component of all synaptic vesicles that is required for normal neurotransmission. Here we report that in intact synaptic terminals SV2 is a phosphoprotein. Phosphopeptide mapping studies indicate that a major site of phosphorylation is located on the cytoplasmic amino terminus. SV2 is phosphorylated on serine and threonine but not on tyrosine residues, indicating that it is a substrate for serine/threonine kinases. Phosphopeptide mapping, in gel kinase assays, and surveys of kinase inhibitors suggest that casein kinase I is a primary SV2 kinase. The amino terminus of SV2 was previously shown to mediate its interaction with synaptotagmin, a calcium-binding protein also required for normal neurotransmission. Comparison of synaptotagmin binding with phosphorylated and unphosphorylated SV2 amino-terminal peptides reveals an increase in binding with phosphorylation. These results suggest that the affinity of SV2 for synaptotagmin is modulated by phosphorylation of SV2.
authors.affiliation: Molecular and Cellular Biology Program, Graduate Program in Neurobiology and Behavior, and Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Pyle
authors.forename: A E
authors.initials: AE
authors.lastname: Schivell
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
authors.forename: S M
authors.initials: SM
authors.lastname: Bajjalieh
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D047388:Casein Kinases; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010449:Peptide Mapping; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D050857:Synaptotagmins
chemical_list: D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C489618:Sv2a protein, rat; D050857:Synaptotagmins; D011494:Protein Kinases; D047388:Casein Kinases