The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans.
Primary ciliary dyskinesia (PCD) is characterized by dysfunction of respiratory cilia and sperm flagella and random determination of visceral asymmetry. Here, we identify the DRC1 subunit of the nexin-dynein regulatory complex (N-DRC), an axonemal structure critical for the regulation of dynein motors, and show that mutations in the gene encoding DRC1, CCDC164, are involved in PCD pathogenesis. Loss-of-function mutations disrupting DRC1 result in severe defects in assembly of the N-DRC structure and defective ciliary movement in Chlamydomonas reinhardtii and humans. Our results highlight a role for N-DRC integrity in regulating ciliary beating and provide the first direct evidence that mutations in DRC genes cause human disease.
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.
Maureen
M
Wirschell
Heike
H
Olbrich
Claudius
C
Werner
Douglas
D
Tritschler
Raqual
R
Bower
Winfield S
WS
Sale
Niki T
NT
Loges
Petra
P
Pennekamp
Sven
S
Lindberg
Unne
U
Stenram
Birgitta
B
Carlén
Elisabeth
E
Horak
Gabriele
G
Köhler
Peter
P
Nürnberg
Gudrun
G
Nürnberg
Mary E
ME
Porter
Heymut
H
Omran
D020418:Algal Proteins / Q000235:genetics*; D000595:Amino Acid Sequence; D056444:Axonemal Dyneins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D054468:Axoneme / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics*; D002696:Chlamydomonas / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002923:Cilia / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002925:Ciliary Motility Disorders / Q000235:genetics / Q000473:pathology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D013082:Sperm Tail / Q000378:metabolism / Q000648:ultrastructure
D020418:Algal Proteins; D002352:Carrier Proteins; C581311:DRC1 protein, human; D008869:Microtubule-Associated Proteins; D017395:Plasminogen Activator Inhibitor 1; D056444:Axonemal Dyneins