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

2013; Nature Portfolio; Volume: 45; Issue: 3 Linguagem: Inglês

10.1038/ng.2533

1546-1718

Maureen Wirschell, Heike Olbrich, Claudius Werner, Douglas Tritschler, Raqual Bower, Winfield S. Sale, Niki T. Loges, Petra Pennekamp, Staffan I. Lindberg, Unne Stenram, Birgitta Carlén, Elisabeth Horak, Gabriele Köhler, Peter Nürnberg, Gudrun Nürnberg, Mary E. Porter, Heymut Omran,

Cerebrospinal fluid and hydrocephalus

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.