title: Kinesin family 17 (osmotic avoidance abnormal-3) is dispensable for photoreceptor morphology and function.
abstract: In Caenorhabditis elegans, homodimeric [kinesin family (KIF) 17, osmotic avoidance abnormal-3 (OSM-3)] and heterotrimeric (KIF3) kinesin-2 motors are required to establish sensory cilia by intraflagellar transport (IFT) where KIF3 and KIF17 cooperate to build the axoneme core and KIF17 builds the distal segments. However, the function of KIF17 in vertebrates is unresolved. We expressed full-length and motorless KIF17 constructs in mouse rod photoreceptors using adeno-associated virus in Xenopus laevis rod photoreceptors using a transgene and in ciliated IMCD3 cells. We found that tagged KIF17 localized along the rod outer segment axoneme when expressed in mouse and X. laevis photoreceptors, whereas KIF3A was restricted to the proximal axoneme. Motorless KIF3A and KIF17 mutants caused photoreceptor degeneration, likely through dominant negative effects on IFT. KIF17 mutant lacking the motor domain translocated to nuclei after exposure of a C-terminal nuclear localization signal. Germ-line deletion of Kif17 in mouse did not affect photoreceptor function. A rod-specific Kif3/Kif17 double knockout mouse demonstrated that KIF17 and KIF3 do not act synergistically and did not prevent rhodopsin trafficking to rod outer segments. In summary, the nematode model of KIF3/KIF17 cooperation apparently does not apply to mouse photoreceptors in which the photosensory cilium is built exclusively by KIF3.
authors.affiliation: *Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, and Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA; and Department of Biology, University of Utah, Salt Lake City, Utah, USA li.jiang@hsc.utah.edu wbaehr@hsc.utah.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: *Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, and Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA; and Department of Biology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Tam
authors.affiliation: *Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, and Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA; and Department of Biology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Ying
authors.affiliation: *Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, and Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA; and Department of Biology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Sen
authors.initials: S
authors.lastname: Wu
authors.affiliation: *Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, and Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA; and Department of Biology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.affiliation: *Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, and Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA; and Department of Biology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Frederick
authors.affiliation: *Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, and Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA; and Department of Biology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Orson L
authors.initials: OL
authors.lastname: Moritz
authors.affiliation: *Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, and Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China; Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA; and Department of Biology, University of Utah, Salt Lake City, Utah, USA li.jiang@hsc.utah.edu wbaehr@hsc.utah.edu.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baehr
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D021381:Protein Transport; D012243:Rhodopsin / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: C409642:KIF17 protein, mouse; D012243:Rhodopsin; D016547:Kinesins
keywords: anterograde intraflagellar transport; kinesin-2 truncation mutants; photoreceptor degeneration; rhodopsin trafficking