title: Inhibition of exocytosis or endocytosis blocks activity-dependent redistribution of synapsin.
abstract: The synaptic vesicle cycle encompasses the pre-synaptic events that drive neurotransmission. Influx of calcium leads to the fusion of synaptic vesicles with the plasma membrane and the release of neurotransmitter, closely followed by endocytosis. Vacated release sites are repopulated with vesicles which are then primed for release. When activity is intense, reserve vesicles may be mobilized to counteract an eventual decline in transmission. Recently, interplay between endocytosis and repopulation of the readily releasable pool of vesicles has been identified. In this study, we show that exo-endocytosis is necessary to enable detachment of synapsin from reserve pool vesicles during synaptic activity. We report that blockage of exocytosis in cultured mouse hippocampal neurons, either by tetanus toxin or by the deletion of munc13, inhibits the activity-dependent redistribution of synapsin from the pre-synaptic terminal into the axon. Likewise, perturbation of endocytosis with dynasore or by a dynamin dominant-negative mutant fully prevents synapsin redistribution. Such inhibition of synapsin redistribution occurred despite the efficient phosphorylation of synapsin at its protein kinase A/CaMKI site, indicating that disengagement of synapsin from the vesicles requires exocytosis and endocytosis in addition to phosphorylation. Our results therefore reveal hitherto unidentified feedback within the synaptic vesicle cycle involving the synapsin-managed reserve pool.
authors: Department of Physiology and Neurobiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors: Ayelet
authors: A
authors: Orenbuch
authors: Orenbuch
authors: O
authors: Ayelet
authors: Yoav
authors: Y
authors: Shulman
authors: Shulman
authors: S
authors: Yoav
authors: Noa
authors: N
authors: Lipstein
authors: Lipstein
authors: L
authors: Noa
authors: Amit
authors: A
authors: Bechar
authors: Bechar
authors: B
authors: Amit
authors: Yotam
authors: Y
authors: Lavy
authors: Lavy
authors: L
authors: Yotam
authors: Eliaz
authors: E
authors: Brumer
authors: Brumer
authors: B
authors: Eliaz
authors: Mariya
authors: M
authors: Vasileva
authors: Vasileva
authors: V
authors: Mariya
authors: Joy
authors: J
authors: Kahn
authors: Kahn
authors: K
authors: Joy
authors: Liza
authors: L
authors: Barki-Harrington
authors: Barki-Harrington
authors: BH
authors: Liza
authors: Thomas
authors: T
authors: Kuner
authors: Kuner
authors: K
authors: Thomas
authors: Daniel
authors: D
authors: Gitler
authors: Gitler
authors: G
authors: Daniel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006835:Hydrazones / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000235:genetics; D016704:Synapsins / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013744:Tetanus Toxin / Q000494:pharmacology; D014162:Transfection / Q000379:methods
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D006835:Hydrazones; D047908:Intracellular Signaling Peptides and Proteins; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D016704:Synapsins; D013744:Tetanus Toxin; C503321:Unc13a protein, mouse; C485549:Unc13b protein, mouse; C485184:enhanced green fluorescent protein; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D049452:Green Fluorescent Proteins; D004533:Egtazic Acid