Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins.
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.
Omran
Heymut
H
Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg Mathildenstrasse 1, D-79106 Freiburg, Germany. heymut.omran@uniklinik-freiburg.de
Kobayashi
Daisuke
D
Olbrich
Heike
H
Tsukahara
Tatsuya
T
Loges
Niki T
NT
Hagiwara
Haruo
H
Zhang
Qi
Q
Leblond
Gerard
G
O'Toole
Eileen
E
Hara
Chikako
C
Mizuno
Hideaki
H
Kawano
Hiroyuki
H
Fliegauf
Manfred
M
Yagi
Toshiki
T
Koshida
Sumito
S
Miyawaki
Atsushi
A
Zentgraf
Hanswalter
H
Seithe
Horst
H
Reinhardt
Richard
R
Watanabe
Yoshinori
Y
Kamiya
Ritsu
R
Mitchell
David R
DR
Takeda
Hiroyuki
H
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
D029941:Fish Proteins; D018840:HSP70 Heat-Shock Proteins; C582728:Ktu protein, mouse; D011506:Proteins; D004398:Dyneins