CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs.
Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.
Unit of Animal Genomics, Groupe Interdisciplinaire de Genomique Appliquee-Recherche (GIGA-R) and Faculty of Veterinary Medicine, University of Liège (B34), Liège, Belgium.
Anne-Christine
AC
Merveille
Erica E
EE
Davis
Anita
A
Becker-Heck
Marie
M
Legendre
Israel
I
Amirav
Géraldine
G
Bataille
John
J
Belmont
Nicole
N
Beydon
Frédéric
F
Billen
Annick
A
Clément
Cécile
C
Clercx
André
A
Coste
Rachelle
R
Crosbie
Jacques
J
de Blic
Stephane
S
Deleuze
Philippe
P
Duquesnoy
Denise
D
Escalier
Estelle
E
Escudier
Manfred
M
Fliegauf
Judith
J
Horvath
Kent
K
Hill
Mark
M
Jorissen
Jocelyne
J
Just
Andreas
A
Kispert
Mark
M
Lathrop
Niki Tomas
NT
Loges
June K
JK
Marthin
Yukihide
Y
Momozawa
Guy
G
Montantin
Kim G
KG
Nielsen
Heike
H
Olbrich
Jean-François
JF
Papon
Isabelle
I
Rayet
Gilles
G
Roger
Miriam
M
Schmidts
Henrique
H
Tenreiro
Jeffrey A
JA
Towbin
Diana
D
Zelenika
Hanswalter
H
Zentgraf
Michel
M
Georges
Anne-Sophie
AS
Lequarré
Nicholas
N
Katsanis
Heymut
H
Omran
Serge
S
Amselem
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology*; D002925:Ciliary Motility Disorders / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004285:Dogs; D004398:Dyneins / Q000235:genetics*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology
C556026:CCDC39 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D004398:Dyneins