title: The zebrafish pob gene encodes a novel protein required for survival of red cone photoreceptor cells.
abstract: The zebrafish mutant, partial optokinetic response b (pob), was isolated using an N-ethyl N-nitrosourea (ENU)-based screening strategy designed to identify larvae with defective optokinetic responses in red but not white light. Previous studies showed that red-light blindness in pob is due to the specific loss of long-wavelength photoreceptor cells via an apoptotic mechanism. Here, we used positional cloning to identify the mutated pob gene. We find that pob encodes a highly conserved 30-kDa protein of unknown function. To demonstrate that the correct gene was isolated, we used the Tol2 transposon system to generate transgenic animals and rescue the mutant phenotype. The Pob protein contains putative transmembrane regions and protein-sorting signals. It is localized to the inner segment and synapse in photoreceptor cells, and when expressed in COS-7 cells it localizes to intracellular compartments. We also show that the degeneration of red cone photoreceptors in the mutants occurs independently of light. On the basis of our findings, we propose that Pob is not involved in phototransduction but rather plays an essential role in protein sorting and/or trafficking.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, 98195, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Taylor
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kikkawa
authors.forename: Antonio
authors.initials: A
authors.lastname: Diez-Juan
authors.forename: Visvanathan
authors.initials: V
authors.lastname: Ramamurthy
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Susan E
authors.initials: SE
authors.lastname: Brockerhoff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000235:genetics; D002522:Chlorocebus aethiops; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D029961:Zebrafish Proteins; C510644:emc3 protein, zebrafish
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