title: Vti1a identifies a vesicle pool that preferentially recycles at rest and maintains spontaneous neurotransmission.
abstract: Recent studies suggest that synaptic vesicles (SVs) giving rise to spontaneous neurotransmission are distinct from those that carry out evoked release. However, the molecular basis of this dichotomy remains unclear. Here, we focused on two noncanonical SNARE molecules, Vps10p-tail-interactor-1a (vti1a) and VAMP7, previously shown to reside on SVs. Using simultaneous multicolor imaging at individual synapses, we could show that compared to the more abundant vesicular SNARE synaptobrevin2, both vti1a and VAMP7 were reluctantly mobilized during activity. Vti1a, but not VAMP7, showed robust trafficking under resting conditions that could be partly matched by synaptobrevin2. Furthermore, loss of vti1a function selectively reduced high-frequency spontaneous neurotransmitter release detected postsynaptically. Expression of a truncated version of vti1a augmented spontaneous release more than full-length vti1a, suggesting that an autoinhibitory process regulates vti1a function. Taken together, these results support the premise that in its native form vti1a selectively maintains spontaneous neurotransmitter release.
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390-9111, USA.
authors.forename: Denise M O
authors.initials: DM
authors.lastname: Ramirez
authors.forename: Mikhail
authors.initials: M
authors.lastname: Khvotchev
authors.forename: Brent
authors.initials: B
authors.lastname: Trauterman
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000235:genetics; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D018942:Macrolides / Q000494:pharmacology; D016253:Microscopy, Immunoelectron / Q000379:methods; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D050863:Synaptotagmin I / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D018942:Macrolides; D050766:Qb-SNARE Proteins; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering; D050600:SNARE Proteins; D050863:Synaptotagmin I; C496926:Vamp7 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; C491417:Vti1a protein, rat; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D011189:Potassium Chloride; C036978:concanamycin A; D002118:Calcium