PMID- 10571231 OWN - NLM STAT- MEDLINE DCOM- 19991206 LR - 20190822 IS - 0896-6273 (Print) IS - 0896-6273 (Linking) VI - 24 IP - 2 DP - 1999 Oct TI - A phospho-switch controls the dynamic association of synapsins with synaptic vesicles. PG - 377-87 AB - 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. FAU - Hosaka, M AU - Hosaka M AD - Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical School, Dallas 75235, USA. FAU - Hammer, R E AU - Hammer RE FAU - Sudhof, T C AU - Sudhof TC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neuron JT - Neuron JID - 8809320 RN - 0 (Phospholipids) RN - 0 (Synapsins) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) SB - IM MH - Amino Acid Sequence/genetics MH - Animals MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Enzyme Activation/physiology MH - Exocytosis/physiology MH - Mice MH - Molecular Sequence Data MH - Phospholipids/metabolism MH - Phosphorylation MH - Rats MH - Substrate Specificity MH - Synapsins/genetics/*metabolism MH - Synaptic Vesicles/*metabolism EDAT- 1999/11/26 00:00 MHDA- 1999/11/26 00:01 CRDT- 1999/11/26 00:00 PHST- 1999/11/26 00:00 [pubmed] PHST- 1999/11/26 00:01 [medline] PHST- 1999/11/26 00:00 [entrez] AID - S0896-6273(00)80851-X [pii] AID - 10.1016/s0896-6273(00)80851-x [doi] PST - ppublish SO - Neuron. 1999 Oct;24(2):377-87. doi: 10.1016/s0896-6273(00)80851-x.