title: Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function.
abstract: Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Cby1, the mammalian orthologue of the Drosophila Chibby protein, localizes to mature centrioles, is important for ciliogenesis in multiciliated airway epithelia in mice, and antagonizes canonical Wnt signaling via direct regulation of β-catenin. We report that deletion of the mouse Cby1 gene results in cystic kidneys, a phenotype common to ciliopathies, and that Cby1 facilitates the formation of primary cilia and ciliary recruitment of the Joubert syndrome protein Arl13b. Localization of Cby1 to the distal end of mature centrioles depends on the centriole protein Ofd1. Superresolution microscopy using both three-dimensional SIM and STED reveals that Cby1 localizes to an ∼250-nm ring at the distal end of the mature centriole, in close proximity to Ofd1 and Ahi1, a component of the transition zone between centriole and cilium. The amount of centriole-localized Ahi1, but not Ofd1, is reduced in Cby1(-/-) cells. This suggests that Cby1 is required for efficient recruitment of Ahi1, providing a possible molecular mechanism for the ciliogenesis defect in Cby1(-/-) cells.
authors.affiliation: Department of Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305.
authors.forename: Yin Loon
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Department of Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305.
authors.forename: Joshua
authors.initials: J
authors.lastname: Santé
authors.affiliation: Department of Chemistry, Stanford School of Medicine, Stanford University, Stanford, CA 94305.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Comerci
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cyge
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Menezes
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Feng-Qian
authors.initials: FQ
authors.lastname: Li
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Germino
authors.affiliation: Department of Chemistry, Stanford School of Medicine, Stanford University, Stanford, CA 94305.
authors.forename: W E
authors.initials: WE
authors.lastname: Moerner
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takemaru
authors.affiliation: Department of Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305 Department of Genetics, Stanford School of Medicine, Stanford University, Stanford, CA 94305 stearns@stanford.edu.
authors.forename: Tim
authors.initials: T
authors.lastname: Stearns
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism*; D002923:Cilia / Q000235:genetics* / Q000473:pathology; D052177:Kidney Diseases, Cystic / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C465818:Ahi1 protein, mouse; C560093:Arl13b protein, mouse; D002352:Carrier Proteins; C517894:Chibby protein, mouse; D009687:Nuclear Proteins; C508360:OFD1 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051176:beta Catenin; D020727:ADP-Ribosylation Factors
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