title: Rab3A mediates vesicle delivery at photoreceptor ribbon synapses.
abstract: Rab3A is a synaptic vesicle-associated protein found throughout the nervous system, but its precise function is unknown. Genetic knock-out studies show that Rab3A is not necessary for vesicular release or replenishment at conventional synapses in the brain. Here we explore the function of Rab3A at ribbon synapses in the retina of the tiger salamander (Ambystoma tigrinum). Fluorescently labeled Rab3A, delivered into rods and cones through a patch pipette, binds to and dissociates from synaptic ribbons. Experiments using nonphosphorylatable GDP analogs and a GTPase-deficient Rab3A mutant indicate that ribbon binding and dissociation are governed by a GTP hydrolysis cycle. Paired recordings from presynaptic photoreceptors and postsynaptic OFF-bipolar cells show that the Rab3A mutant blocks synaptic release in an activity-dependent manner, with more frequent stimulation leading to more rapid block. The frequency dependence of block by exogenous Rab3A suggests that it acts competitively with synaptic vesicles to interfere with their resupply to release sites. Together, these findings suggest a crucial role of Rab3A in delivering vesicles to Ca²⁺-dependent release sites at ribbon synapses.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Tian
authors.forename: C Shan
authors.initials: CS
authors.lastname: Xu
authors.forename: Rachel
authors.initials: R
authors.lastname: Montpetit
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kramer
mesh_terms: D000557:Ambystoma; D000818:Animals; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D008297:Male; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*; D020826:rab3A GTP-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D020558:GTP Phosphohydrolases; D020826:rab3A GTP-Binding Protein