title: Retinophilin is a light-regulated phosphoprotein required to suppress photoreceptor dark noise in Drosophila.
abstract: Photoreceptor cells achieve high sensitivity, reliably detecting single photons, while limiting the spontaneous activation events responsible for dark noise. We used proteomic, genetic, and electrophysiological approaches to characterize Retinophilin (RTP) (CG10233) in Drosophila photoreceptors and establish its involvement in dark-noise suppression. RTP possesses membrane occupation and recognition nexus (MORN) motifs, a structure shared with mammalian junctophilins and other membrane-associated proteins found within excitable cells. We show the MORN repeats, and both the N- and C-terminal domains, are required for RTP localization in the microvillar light-gathering organelle, the rhabdomere. RTP exists in multiple phosphorylated isoforms under dark conditions and is dephosphorylated by light exposure. An RTP deletion mutant exhibits a high rate of spontaneous membrane depolarization events in dark conditions but retains the normal kinetics of the light response. Photoreceptors lacking neither inactivation nor afterpotential C (NINAC) myosin III, a motor protein/kinase, also display a similar dark-noise phenotype as the RTP deletion. We show that NINAC mutants are depleted for RTP. These results suggest the increase in dark noise in NINAC mutants is attributable to lack of RTP and, furthermore, defines a novel role for NINAC in the rhabdomere. We propose that RTP is a light-regulated phosphoprotein that organizes rhabdomeric components to suppress random activation of the phototransduction cascade and thus increases the signaling fidelity of dark-adapted photoreceptors.
authors.affiliation: Indiana University South Bend, South Bend, Indiana 46615, USA.
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Mecklenburg
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takemori
authors.forename: Naoka
authors.initials: N
authors.lastname: Komori
authors.forename: Brian
authors.initials: B
authors.lastname: Chu
authors.forename: Roger C
authors.initials: RC
authors.lastname: Hardie
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Joseph E
authors.initials: JE
authors.lastname: O'Tousa
mesh_terms: D000221:Adaptation, Ocular / Q000502:physiology / Q000528:radiation effects; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D003623:Dark Adaptation / Q000502:physiology / Q000528:radiation effects*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005123:Eye / Q000378:metabolism* / Q000648:ultrastructure; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D008871:Microvilli / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D017434:Protein Structure, Tertiary / Q000502:physiology / Q000528:radiation effects; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D010750:Phosphoproteins; C520357:rtp protein, Drosophila