title: Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation.
abstract: Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking the basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting in chronic airway infection. In this paper, using primary cultures of mouse tracheal epithelial cells, we show that Cby facilitates basal body docking to the apical cell membrane through proper formation of ciliary vesicles at the distal appendage during the early stages of ciliogenesis. Cby is recruited to the distal appendages of centrioles via physical interaction with the distal appendage protein CEP164. Cby then associates with the membrane trafficking machinery component Rabin8, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rab8, to promote recruitment of Rab8 and efficient assembly of ciliary vesicles. Thus, our study identifies Cby as a key regulator of ciliary vesicle formation and basal body docking during the differentiation of airway ciliated cells.
authors.affiliation: Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794 Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Burke
authors.affiliation: Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794 Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Feng-Qian
authors.initials: FQ
authors.lastname: Li
authors.affiliation: Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cyge
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arashiro
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Heath, Denver, CO 80206.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Brechbuhl
authors.affiliation: Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794 Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Saul S
authors.initials: SS
authors.lastname: Siller
authors.affiliation: Laboratory of Cell and Developmental Signaling, National Cancer Institute, Frederick, MD 21072.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Weiss
authors.affiliation: Nikon Instruments, Inc., Melville, NY 11747.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: O'Connell
authors.affiliation: Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Damon
authors.initials: D
authors.lastname: Love
authors.affiliation: Laboratory of Cell and Developmental Signaling, National Cancer Institute, Frederick, MD 21072.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Westlake
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Heath, Denver, CO 80206.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Reynolds
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kuriyama
authors.affiliation: Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794 Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794 Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794 Graduate Program in Genetics, Medical Scientist Training Program, Graduate Program in Molecular and Cellular Pharmacology, and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794 ken-ichi.takemaru@stonybrook.edu.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takemaru
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D064652:Basal Bodies / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002502:Centrioles / Q000502:physiology; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology*; D000081410:Germinal Center Kinases; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D009079:Mucociliary Clearance / Q000235:genetics; D009281:Naphthalenes; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D020545:Respiratory Mucosa / Q000166:cytology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: C524694:CEP164 protein, human; D002352:Carrier Proteins; C517894:Chibby protein, mouse; D000081410:Germinal Center Kinases; D008868:Microtubule Proteins; D009281:Naphthalenes; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C521976:Rab8 protein, mouse; C031721:naphthalene; D017346:Protein Serine-Threonine Kinases; D020691:rab GTP-Binding Proteins