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

Nat Genet. 2013 Mar;45(3):262-8. doi: 10.1038/ng.2533. Epub 2013 Jan 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algal Proteins / genetics*
  • Amino Acid Sequence
  • Axonemal Dyneins / genetics
  • Axonemal Dyneins / metabolism
  • Axonemal Dyneins / ultrastructure
  • Axoneme / genetics
  • Axoneme / metabolism
  • Axoneme / ultrastructure
  • Carrier Proteins / genetics*
  • Chlamydomonas* / genetics
  • Chlamydomonas* / metabolism
  • Chlamydomonas* / ultrastructure
  • Cilia* / genetics
  • Cilia* / metabolism
  • Cilia* / ultrastructure
  • Ciliary Motility Disorders* / genetics
  • Ciliary Motility Disorders* / pathology
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism
  • Humans
  • Kartagener Syndrome* / genetics
  • Kartagener Syndrome* / metabolism
  • Kartagener Syndrome* / physiopathology
  • Male
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Sperm Tail / metabolism
  • Sperm Tail / ultrastructure

Substances

  • Algal Proteins
  • Carrier Proteins
  • DRC1 protein, human
  • Microtubule-Associated Proteins
  • Plasminogen Activator Inhibitor 1
  • Axonemal Dyneins

Associated data

  • GENBANK/AFU81554
  • GENBANK/JX311620
  • RefSeq/NP_659475