title: Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins.
abstract: Cilia and flagella are highly conserved organelles that have diverse roles in cell motility and sensing extracellular signals. Motility defects in cilia and flagella often result in primary ciliary dyskinesia. However, the mechanisms underlying cilia formation and function, and in particular the cytoplasmic assembly of dyneins that power ciliary motility, are only poorly understood. Here we report a new gene, kintoun (ktu), involved in this cytoplasmic process. This gene was first identified in a medaka mutant, and found to be mutated in primary ciliary dyskinesia patients from two affected families as well as in the pf13 mutant of Chlamydomonas. In the absence of Ktu/PF13, both outer and inner dynein arms are missing or defective in the axoneme, leading to a loss of motility. Biochemical and immunohistochemical studies show that Ktu/PF13 is one of the long-sought proteins involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg Mathildenstrasse 1, D-79106 Freiburg, Germany. heymut.omran@uniklinik-freiburg.de
authors.forename: Heymut
authors.initials: H
authors.lastname: Omran
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Heike
authors.initials: H
authors.lastname: Olbrich
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Tsukahara
authors.forename: Niki T
authors.initials: NT
authors.lastname: Loges
authors.forename: Haruo
authors.initials: H
authors.lastname: Hagiwara
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Gerard
authors.initials: G
authors.lastname: Leblond
authors.forename: Eileen
authors.initials: E
authors.lastname: O'Toole
authors.forename: Chikako
authors.initials: C
authors.lastname: Hara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mizuno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawano
authors.forename: Manfred
authors.initials: M
authors.lastname: Fliegauf
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yagi
authors.forename: Sumito
authors.initials: S
authors.lastname: Koshida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyawaki
authors.forename: Hanswalter
authors.initials: H
authors.lastname: Zentgraf
authors.forename: Horst
authors.initials: H
authors.lastname: Seithe
authors.forename: Richard
authors.initials: R
authors.lastname: Reinhardt
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Ritsu
authors.initials: R
authors.lastname: Kamiya
authors.forename: David R
authors.initials: DR
authors.lastname: Mitchell
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
mesh_terms: D000818:Animals; D054468:Axoneme / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002696:Chlamydomonas / Q000235:genetics / Q000378:metabolism; D002923:Cilia / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003001:Cloning, Molecular; D004398:Dyneins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D005808:Genes, Recessive / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009990:Oryzias / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013081:Sperm Motility; D013737:Testis / Q000166:cytology
chemical_list: D029941:Fish Proteins; D018840:HSP70 Heat-Shock Proteins; C582728:Ktu protein, mouse; D011506:Proteins; D004398:Dyneins