title: ATP binding to synaspsin IIa regulates usage and clustering of vesicles in terminals of hippocampal neurons.
abstract: Synaptic transmission is expensive in terms of its energy demands and was recently shown to decrease the ATP concentration within presynaptic terminals transiently, an observation that we confirm. We hypothesized that, in addition to being an energy source, ATP may modulate the synapsins directly. Synapsins are abundant neuronal proteins that associate with the surface of synaptic vesicles and possess a well defined ATP-binding site of undetermined function. To examine our hypothesis, we produced a mutation (K270Q) in synapsin IIa that prevents ATP binding and reintroduced the mutant into cultured mouse hippocampal neurons devoid of all synapsins. Remarkably, staining for synaptic vesicle markers was enhanced in these neurons compared with neurons expressing wild-type synapsin IIa, suggesting overly efficient clustering of vesicles. In contrast, the mutation completely disrupted the capability of synapsin IIa to slow synaptic depression during sustained 10 Hz stimulation, indicating that it interfered with synapsin-dependent vesicle recruitment. Finally, we found that the K270Q mutation attenuated the phosphorylation of synapsin IIa on a distant PKA/CaMKI consensus site known to be essential for vesicle recruitment. We conclude that ATP binding to synapsin IIa plays a key role in modulating its function and in defining its contribution to hippocampal short-term synaptic plasticity.
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel, and.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Shulman
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel, and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stavsky
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and Sagol School of Neuroscience, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Tatiana
authors.identifier: http://orcid.org/0000-0002-4740-7436
authors.initials: T
authors.lastname: Fedorova
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, and.
authors.forename: Dan
authors.initials: D
authors.lastname: Mikulincer
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, and.
authors.forename: Merav
authors.initials: M
authors.lastname: Atias
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, and.
authors.forename: Igal
authors.initials: I
authors.lastname: Radinsky
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, and.
authors.forename: Joy
authors.initials: J
authors.lastname: Kahn
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and Sagol School of Neuroscience, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Inna
authors.initials: I
authors.lastname: Slutsky
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences, and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel, and gitler@bgu.ac.il.
authors.forename: Daniel
authors.identifier: http://orcid.org/0000-0001-9544-3610
authors.initials: D
authors.lastname: Gitler
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D016704:Synapsins; D000255:Adenosine Triphosphate
keywords: ATP; phosphorylation; short-term plasticity; synapsin; synaptic vesicle; vesicle pools