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PMID: 23354437 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans.

Nature genetics ·Vol. 45 ·No. 3 ·2013-03-00 ·Pages 262-8

Wirschell M, Olbrich H, Werner C, Tritschler D, Bower R, Sale WS, Loges NT, Pennekamp P, Lindberg S, Stenram U, Carlén B, Horak E, Köhler G, Nürnberg P, Nürnberg G, Porter ME, Omran H

Abstract

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.

MeSH Terms
Algal Proteins/genetics Amino Acid Sequence Axonemal Dyneins/genetics,metabolism,ultrastructure Axoneme/genetics,metabolism,ultrastructure Carrier Proteins/genetics Chlamydomonas/genetics,metabolism,ultrastructure Cilia/genetics,metabolism,ultrastructure Ciliary Motility Disorders/genetics,pathology Cytoskeleton/genetics,metabolism Humans Kartagener Syndrome/genetics,metabolism,physiopathology Male Microtubule-Associated Proteins/genetics,metabolism Molecular Sequence Data Mutation Plasminogen Activator Inhibitor 1/genetics,metabolism Sperm Tail/metabolism,ultrastructure
Chemicals
Algal Proteins Carrier Proteins DRC1 protein, human Microtubule-Associated Proteins Plasminogen Activator Inhibitor 1 Axonemal Dyneins
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Wirschell Maureen
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.
Olbrich Heike
Werner Claudius
Tritschler Douglas
Bower Raqual
Sale Winfield S
Loges Niki T
Pennekamp Petra
Lindberg Sven
Stenram Unne
Carlén Birgitta
Horak Elisabeth
Köhler Gabriele
Nürnberg Peter
Nürnberg Gudrun
Porter Mary E
Omran Heymut
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.2533
Published
2013-03-00
Epub
2013-00-27
Pages
262-8
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3818796
Subset
IM
Grants
NIGMS NIH HHS · R01 GM051173 · United States
NIGMS NIH HHS · GM-55667 · United States
NIGMS NIH HHS · GM-051173 · United States
NIGMS NIH HHS · GM-075446 · United States
NIGMS NIH HHS · F32 GM075446 · United States
NIGMS NIH HHS · R37 GM055667 · United States
NIGMS NIH HHS · R37 GM051173 · United States
NIGMS NIH HHS · R01 GM055667 · United States
Databases
GENBANK
AFU81554, JX311620
RefSeq
NP_659475
External Links
PubMed source DOI: 10.1038/ng.2533 PMC Full Text View journal details
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