title: RIBEYE, a component of synaptic ribbons: a protein's journey through evolution provides insight into synaptic ribbon function.
abstract: Photoreceptor cells utilize ribbon synapses to transmit sensory signals at high resolution. Ribbon synapses release neurotransmitters tonically, with a high release rate made possible by continuous docking of synaptic vesicles on presynaptic ribbons. We have partially purified synaptic ribbons from retina and identified a major protein component called RIBEYE. RIBEYE is composed of a unique A domain specific for ribbons, and a B domain identical with CtBP2, a transcriptional repressor that in turn is related to 2-hydroxyacid dehydrogenases. The A domain mediates assembly of RIBEYE into large structures, whereas the B domain binds NAD(+) with high affinity, similar to 2-hydroxyacid dehydrogenases. Our results define a unique component of synaptic ribbons and suggest that RIBEYE evolved in vertebrates under utilization of a preexisting protein to build a unique scaffold for a specialized synapse.
authors.affiliation: Howard Hughes Medical Institute, Center for Basic Neuroscience, Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: F
authors.initials: F
authors.lastname: Schmitz
authors.forename: A
authors.initials: A
authors.lastname: Königstorfer
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D015388:Organelles / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics; D012160:Retina / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D014162:Transfection
chemical_list: D056970:Co-Repressor Proteins; C486016:Ctbp2 protein, rat; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D009243:NAD; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human; C083779:2-hydroxyacid dehydrogenase