title: Synaptotagmin 7 functions as a Ca2+-sensor for synaptic vesicle replenishment.
abstract: Synaptotagmin (syt) 7 is one of three syt isoforms found in all metazoans; it is ubiquitously expressed, yet its function in neurons remains obscure. Here, we resolved Ca(2+)-dependent and Ca(2+)-independent synaptic vesicle (SV) replenishment pathways, and found that syt 7 plays a selective and critical role in the Ca(2+)-dependent pathway. Mutations that disrupt Ca(2+)-binding to syt 7 abolish this function, suggesting that syt 7 functions as a Ca(2+)-sensor for replenishment. The Ca(2+)-binding protein calmodulin (CaM) has also been implicated in SV replenishment, and we found that loss of syt 7 was phenocopied by a CaM antagonist. Moreover, we discovered that syt 7 binds to CaM in a highly specific and Ca(2+)-dependent manner; this interaction requires intact Ca(2+)-binding sites within syt 7. Together, these data indicate that a complex of two conserved Ca(2+)-binding proteins, syt 7 and CaM, serve as a key regulator of SV replenishment in presynaptic nerve terminals. DOI: http://dx.doi.org/10.7554/eLife.01524.001.
authors.affiliation: Department of Neuroscience, Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, United States.
authors.forename: Huisheng
authors.initials: H
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Enfu
authors.initials: E
authors.lastname: Hui
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Chantell S
authors.initials: CS
authors.lastname: Evans
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.forename: Sung E
authors.initials: SE
authors.lastname: Kwon
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chapman
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D009435:Synaptic Transmission / Q000187:drug effects; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D050857:Synaptotagmins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002147:Calmodulin; C494303:Syt7 protein, mouse; D050857:Synaptotagmins; D002118:Calcium
keywords: neurotranmission; synaptic vesicle; synaptotagmin