Document Detail


The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans.
MedLine Citation:
PMID:  23354437     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Maureen Wirschell; Heike Olbrich; Claudius Werner; Douglas Tritschler; Raqual Bower; Winfield S Sale; Niki T Loges; Petra Pennekamp; Sven Lindberg; Unne Stenram; Birgitta Carlén; Elisabeth Horak; Gabriele Köhler; Peter Nürnberg; Gudrun Nürnberg; Mary E Porter; Heymut Omran
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Publication Detail:
Type:  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.     Date:  2013-01-27
Journal Detail:
Title:  Nature genetics     Volume:  45     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-05-30     Revised Date:  2013-11-13    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  262-8     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AFU81554;  JX311620; RefSeq/NP_659475
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MeSH Terms
Descriptor/Qualifier:
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
Grant Support
ID/Acronym/Agency:
GM-051173/GM/NIGMS NIH HHS; GM-075446/GM/NIGMS NIH HHS; GM-55667/GM/NIGMS NIH HHS; R01 GM051173/GM/NIGMS NIH HHS; R37 GM055667/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Algal Proteins; 0/Carrier Proteins; 0/DRC1 protein, human; 0/Microtubule-Associated Proteins; 0/Plasminogen Activator Inhibitor 1; EC 3.6.4.2/Axonemal Dyneins
Comments/Corrections

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