title: How to make a synaptic ribbon: RIBEYE deletion abolishes ribbons in retinal synapses and disrupts neurotransmitter release.
abstract: Synaptic ribbons are large proteinaceous scaffolds at the active zone of ribbon synapses that are specialized for rapid sustained synaptic vesicles exocytosis. A single ribbon-specific protein is known, RIBEYE, suggesting that ribbons may be constructed from RIBEYE protein. RIBEYE knockdown in zebrafish, however, only reduced but did not eliminate ribbons, indicating a more ancillary role. Here, we show in mice that full deletion of RIBEYE abolishes all presynaptic ribbons in retina synapses. Using paired recordings in acute retina slices, we demonstrate that deletion of RIBEYE severely impaired fast and sustained neurotransmitter release at bipolar neuron/AII amacrine cell synapses and rendered spontaneous miniature release sensitive to the slow Ca(2+)-buffer EGTA, suggesting that synaptic ribbons mediate nano-domain coupling of Ca(2+) channels to synaptic vesicle exocytosis. Our results show that RIBEYE is essential for synaptic ribbons as such, and may organize presynaptic nano-domains that position release-ready synaptic vesicles adjacent to Ca(2+) channels.
authors.affiliation: Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute Stanford University School of Medicine, Stanford, CA, USA Department of Neuroanatomy, Institute for Anatomy and Cell Biology Medical School Saarland University, Homburg/Saar, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Maxeiner
authors.affiliation: Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Fujun
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Tan
authors.affiliation: Department of Neuroanatomy, Institute for Anatomy and Cell Biology Medical School Saarland University, Homburg/Saar, Germany tcs1@stanford.edu frank.schmitz@uks.eu.
authors.forename: Frank
authors.initials: F
authors.lastname: Schmitz
authors.affiliation: Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute Stanford University School of Medicine, Stanford, CA, USA tcs1@stanford.edu frank.schmitz@uks.eu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000429:Alcohol Oxidoreductases; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D008297:Male; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D015220:Calcium Channels; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse; D002118:Calcium
keywords: CtBP2; GCamP3; RIBEYE knockout; photoreceptors; tonic release