title: RIBEYE recruits Munc119, a mammalian ortholog of the Caenorhabditis elegans protein unc119, to synaptic ribbons of photoreceptor synapses.
abstract: Munc119 (also denoted as RG4) is a mammalian ortholog of the Caenorhabditis elegans protein unc119 and is essential for vision and synaptic transmission at photoreceptor ribbon synapses by unknown molecular mechanisms. Munc119/RG4 is related to the prenyl-binding protein PrBP/delta and expressed at high levels in photoreceptor ribbon synapses. Synaptic ribbons are presynaptic specializations in the active zone of these tonically active synapses and contain RIBEYE as a unique and major component. In the present study, we identified Munc119 as a RIBEYE-interacting protein at photoreceptor ribbon synapses using five independent approaches. The PrBP/delta homology domain of Munc119 is essential for the interaction with the NADH binding region of RIBEYE(B) domain. But RIBEYE-Munc119 interaction does not depend on NADH binding. A RIBEYE point mutant (RE(B)E844Q) that no longer interacted with Munc119 still bound NADH, arguing that binding of Munc119 and NADH to RIBEYE are independent from each other. Our data indicate that Munc119 is a synaptic ribbon-associated component. We show that Munc119 can be recruited to synaptic ribbons via its interaction with RIBEYE. Our data suggest that the RIBEYE-Munc119 interaction is essential for synaptic transmission at the photoreceptor ribbon synapse.
authors.affiliation: Department of Neuroanatomy, Institute for Anatomy and Cell Biology, Saarland University, Medical School Homburg/Saar, 66421 Homburg/Saar, Germany.
authors.forename: Kannan
authors.initials: K
authors.lastname: Alpadi
authors.forename: Venkat Giri
authors.initials: VG
authors.lastname: Magupalli
authors.forename: Stefanie
authors.initials: S
authors.lastname: Käppel
authors.forename: Louise
authors.initials: L
authors.lastname: Köblitz
authors.forename: Karin
authors.initials: K
authors.lastname: Schwarz
authors.forename: Gail M
authors.initials: GM
authors.lastname: Seigel
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Sung
authors.forename: Frank
authors.initials: F
authors.lastname: Schmitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D014785:Vision, Ocular / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; C098176:UNC-119 protein, C elegans