Home LiteratureArticle Details
PMID: 19052621 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneins.

Nature ·Vol. 456 ·No. 7222 ·2008-12-04 ·Pages 611-6

Omran H, Kobayashi D, Olbrich H, Tsukahara T, Loges NT, Hagiwara H, Zhang Q, Leblond G, O'Toole E, Hara C, Mizuno H, Kawano H, Fliegauf M, Yagi T, Koshida S, Miyawaki A, Zentgraf H, Seithe H, Reinhardt R, Watanabe Y, Kamiya R, Mitchell DR, Takeda H

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.

MeSH Terms
Animals Axoneme/chemistry,genetics,metabolism,pathology Chlamydomonas/genetics,metabolism Cilia/chemistry,genetics,metabolism,pathology Cloning, Molecular Dyneins/metabolism Epithelial Cells/cytology Fish Proteins/genetics,metabolism Genes, Recessive/genetics HSP70 Heat-Shock Proteins/metabolism Humans Kartagener Syndrome/genetics,pathology Male Mice Molecular Sequence Data Mutation/genetics Oryzias/embryology,genetics,metabolism Protein Binding Proteins/genetics,metabolism Sequence Homology, Amino Acid Sperm Motility Testis/cytology
Chemicals
Fish Proteins HSP70 Heat-Shock Proteins Ktu protein, mouse Proteins Dyneins
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Omran Heymut
Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg Mathildenstrasse 1, D-79106 Freiburg, Germany. [email protected]
Kobayashi Daisuke
Olbrich Heike
Tsukahara Tatsuya
Loges Niki T
Hagiwara Haruo
Zhang Qi
Leblond Gerard
O'Toole Eileen
Hara Chikako
Mizuno Hideaki
Kawano Hiroyuki
Fliegauf Manfred
Yagi Toshiki
Koshida Sumito
Miyawaki Atsushi
Zentgraf Hanswalter
Seithe Horst
Reinhardt Richard
Watanabe Yoshinori
Kamiya Ritsu
Mitchell David R
Takeda Hiroyuki
References (46)
46 references, click to expand
  1. Mutant analyses reveal different functions of fgfr1 in medaka and zebrafish despite conserved ligand-receptor relationships.
    Dev Biol. 2007 Apr 1;304(1):326-37 PMID: 17261279
  2. Polycystic kidney disease.
    N Engl J Med. 2004 Jan 8;350(2):151-64 PMID: 14711914
  3. The Chlamydomonas genome reveals the evolution of key animal and plant functions.
    Science. 2007 Oct 12;318(5848):245-50 PMID: 17932292
  4. Characterization of Saccharomyces cerevisiae Nop17p, a novel Nop58p-interacting protein that is involved in Pre-rRNA processing.
    J Mol Biol. 2005 Feb 18;346(2):437-55 PMID: 15670595
  5. Mutations at twelve independent loci result in absence of outer dynein arms in Chylamydomonas reinhardtii.
    J Cell Biol. 1988 Dec;107(6 Pt 1):2253-8 PMID: 2974040
  6. Characterization of a Chlamydomonas insertional mutant that disrupts flagellar central pair microtubule-associated structures.
    J Cell Biol. 1999 Jan 25;144(2):293-304 PMID: 9922455
  7. Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant.
    Kidney Int. 2005 Jul;68(1):23-34 PMID: 15954893
  8. Cloning of flagellar genes in Chlamydomonas reinhardtii by DNA insertional mutagenesis.
    Genetics. 1993 Oct;135(2):375-84 PMID: 8244002
  9. Molecular motors and mechanisms of directional transport in neurons.
    Nat Rev Neurosci. 2005 Mar;6(3):201-14 PMID: 15711600
  10. Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut.
    Development. 2005 Mar;132(6):1247-60 PMID: 15716348
  11. Medaka--a model organism from the far East.
    Nat Rev Genet. 2002 Jan;3(1):53-64 PMID: 11823791
  12. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects.
    Am J Respir Crit Care Med. 2006 Jul 15;174(2):120-6 PMID: 16627867
  13. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome.
    Hum Genet. 2006 Sep;120(2):171-8 PMID: 16783569
  14. When cilia go bad: cilia defects and ciliopathies.
    Nat Rev Mol Cell Biol. 2007 Nov;8(11):880-93 PMID: 17955020
  15. Characterization of monoclonal antibodies against Chlamydomonas flagellar dyneins by high-resolution protein blotting.
    Proc Natl Acad Sci U S A. 1985 Jul;82(14):4717-21 PMID: 3161075
  16. Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis.
    Development. 2005 Apr;132(8):1907-21 PMID: 15790966
  17. ODA16p, a Chlamydomonas flagellar protein needed for dynein assembly.
    Mol Biol Cell. 2005 Oct;16(10):5004-12 PMID: 16093345
  18. The light chain p28 associates with a subset of inner dynein arm heavy chains in Chlamydomonas axonemes.
    Mol Biol Cell. 1995 Jun;6(6):697-711 PMID: 7579689
  19. The medaka draft genome and insights into vertebrate genome evolution.
    Nature. 2007 Jun 7;447(7145):714-9 PMID: 17554307
  20. Genetic defects in ciliary structure and function.
    Annu Rev Physiol. 2007;69:423-50 PMID: 17059358
  21. The role of preassembled cytoplasmic complexes in assembly of flagellar dynein subunits.
    Mol Biol Cell. 1998 Sep;9(9):2337-47 PMID: 9725897
  22. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry.
    Nat Genet. 2002 Feb;30(2):143-4 PMID: 11788826
  23. Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia.
    Am J Respir Crit Care Med. 2005 Jun 15;171(12):1343-9 PMID: 15750039
  24. A systematic genome-wide screen for mutations affecting organogenesis in Medaka, Oryzias latipes.
    Mech Dev. 2004 Jul;121(7-8):647-58 PMID: 15210174
  25. Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination.
    Cell. 2005 May 20;121(4):633-644 PMID: 15907475
  26. The initiation codon determines the efficiency but not the site of translation initiation in Chlamydomonas chloroplasts.
    Plant Cell. 1995 Aug;7(8):1295-305 PMID: 7549485
  27. Intraflagellar transport.
    Nat Rev Mol Cell Biol. 2002 Nov;3(11):813-25 PMID: 12415299
  28. Arrangement of inner dynein arms in wild-type and mutant flagella of Chlamydomonas.
    J Cell Biol. 1992 Sep;118(5):1145-62 PMID: 1387403
  29. Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia.
    Am J Hum Genet. 1999 Dec;65(6):1508-19 PMID: 10577904
  30. Paralyzed flagella mutants of Chlamydomonas reinhardtii. Defective for axonemal doublet microtubule arms.
    J Biol Chem. 1979 Apr 25;254(8):3091-9 PMID: 429335
  31. Functional diversity of axonemal dyneins as studied in Chlamydomonas mutants.
    Int Rev Cytol. 2002;219:115-55 PMID: 12211628
  32. ATP production in Chlamydomonas reinhardtii flagella by glycolytic enzymes.
    Mol Biol Cell. 2005 Oct;16(10):4509-18 PMID: 16030251
  33. Protein-protein interactions in the 18S ATPase of Chlamydomonas outer dynein arms.
    Cell Motil Cytoskeleton. 1986;6(5):510-20 PMID: 2947699
  34. A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia.
    Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3336-41 PMID: 17360648
  35. More than folding: localized functions of cytosolic chaperones.
    Trends Biochem Sci. 2003 Oct;28(10):541-7 PMID: 14559183
  36. Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia.
    Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10282-6 PMID: 12142464
  37. A novel subunit of axonemal dynein conserved among lower and higher eukaryotes.
    FEBS Lett. 2006 Nov 27;580(27):6357-60 PMID: 17094970
  38. Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation.
    J Cell Biol. 2008 Feb 11;180(3):563-78 PMID: 18268103
  39. The Mr 140,000 intermediate chain of Chlamydomonas flagellar inner arm dynein is a WD-repeat protein implicated in dynein arm anchoring.
    Mol Biol Cell. 1998 Dec;9(12):3335-49 PMID: 9843573
  40. A family with RP3 type of X-linked retinitis pigmentosa: an association with ciliary abnormalities.
    Hum Genet. 1992 Jan;88(3):331-4 PMID: 1733835
  41. The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery.
    J Cell Biol. 2008 Feb 11;180(3):579-95 PMID: 18268104
  42. An axonemal dynein particularly important for flagellar movement at high viscosity. Implications from a new Chlamydomonas mutant deficient in the dynein heavy chain gene DHC9.
    J Biol Chem. 2005 Dec 16;280(50):41412-20 PMID: 16236707
  43. Differential light chain assembly influences outer arm dynein motor function.
    Mol Biol Cell. 2005 Dec;16(12):5661-74 PMID: 16195342
  44. ODA16 aids axonemal outer row dynein assembly through an interaction with the intraflagellar transport machinery.
    J Cell Biol. 2008 Oct 20;183(2):313-22 PMID: 18852297
  45. Right-elevated expression of charon is regulated by fluid flow in medaka Kupffer's vesicle.
    Dev Growth Differ. 2007 Jun;49(5):395-405 PMID: 17547649
  46. Functional analysis of an individual IFT protein: IFT46 is required for transport of outer dynein arms into flagella.
    J Cell Biol. 2007 Feb 26;176(5):653-65 PMID: 17312020
Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature07471
Email
[email protected]
Published
2008-12-04
Pages
611-6
Language
English
Region
England
NLM ID
0410462
PMCID
PMC3279746
Subset
IM
Grants
NIGMS NIH HHS · R01 GM044228 · United States
NIGMS NIH HHS · R01 GM044228-17 · United States
NIGMS NIH HHS · GM44228 · United States
Databases
GENBANK
AB455237, AB455535, AB455811, FJ158843, FJ160770
Corrections
CommentIn
PMID: 19492356
External Links
PubMed source DOI: 10.1038/nature07471 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2