title: Stabilization of spontaneous neurotransmitter release at ribbon synapses by ribbon-specific subtypes of complexin.
abstract: Ribbon synapses of tonically releasing sensory neurons must provide a large pool of releasable vesicles for sustained release, while minimizing spontaneous release in the absence of stimulation. Complexins are presynaptic proteins that may accomplish this dual task at conventional synapses by interacting with the molecular machinery of synaptic vesicle fusion at the active zone to retard spontaneous vesicle exocytosis yet facilitate release evoked by depolarization. However, ribbon synapses of photoreceptor cells and bipolar neurons in the retina express distinct complexin subtypes, perhaps reflecting the special requirements of these synapses for tonic release. To investigate the role of ribbon-specific complexins in transmitter release, we combined presynaptic voltage clamp, fluorescence imaging, electron microscopy, and behavioral assays of photoreceptive function in zebrafish. Acute interference with complexin function using a peptide derived from the SNARE-binding domain increased spontaneous synaptic vesicle fusion at ribbon synapses of retinal bipolar neurons without affecting release triggered by depolarization. Knockdown of complexin by injection of an antisense morpholino into zebrafish embryos prevented photoreceptor-driven migration of pigment in skin melanophores and caused the pigment distribution to remain in the dark-adapted state even when embryos were exposed to light. This suggests that loss of complexin function elevated spontaneous release in illuminated photoreceptors sufficiently to mimic the higher release rate normally associated with darkness, thus interfering with visual signaling. We conclude that visual system-specific complexins are required for proper illumination-dependent modulation of the rate of neurotransmitter release at visual system ribbon synapses.
authors: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York 11794-5230, USA.
authors: Thirumalini
authors: T
authors: Vaithianathan
authors: George
authors: G
authors: Zanazzi
authors: Diane
authors: D
authors: Henry
authors: Wendy
authors: W
authors: Akmentin
authors: Gary
authors: G
authors: Matthews
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D003623:Dark Adaptation / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008547:Melanophores / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012160:Retina / Q000166:cytology; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000502:physiology*; D050600:SNARE Proteins / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology; D015027:Zebrafish
chemical_list: D002614:Chelating Agents; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D020319:Oligodeoxyribonucleotides, Antisense; D050600:SNARE Proteins
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