title: Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival.
abstract: Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.
authors.affiliation: Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Omori
authors.forename: Taro
authors.initials: T
authors.lastname: Chaya
authors.forename: Kimiko
authors.initials: K
authors.lastname: Katoh
authors.forename: Naoko
authors.initials: N
authors.lastname: Kajimura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.forename: Koichiro
authors.initials: K
authors.lastname: Muraoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Ueno
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Koyasu
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D005260:Female; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D055212:Photoreceptor Connecting Cilium / Q000378:metabolism* / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism* / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
chemical_list: D008869:Microtubule-Associated Proteins; C497821:RP1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C509962:Mak protein, mouse