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Mol Biol Cell. 2018 Jan 15;29(2):137-153. doi: 10.1091/mbc.E17-08-0510. Epub 2017 Nov 22.

DRC2/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility.

Author information

1
Department of Genetics, Cell Biology, and Development, University of Minnesota Medical School, Minneapolis, MN 55455.
2
Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454.
3
Vienna Biocenter Core Facilities, 1030 Vienna, Austria.
4
Departments of Cell Biology and Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
5
Department of Genetics, Cell Biology, and Development, University of Minnesota Medical School, Minneapolis, MN 55455 porte001@umn.edu.

Abstract

The nexin-dynein regulatory complex (N-DRC) plays a central role in the regulation of ciliary and flagellar motility. In most species, the N-DRC contains at least 11 subunits, but the specific function of each subunit is unknown. Mutations in three subunits (DRC1, DRC2/CCDC65, DRC4/GAS8) have been linked to defects in ciliary motility in humans and lead to a ciliopathy known as primary ciliary dyskinesia (PCD). Here we characterize the biochemical, structural, and motility phenotypes of two mutations in the DRC2 gene of Chlamydomonas Using high-resolution proteomic and structural approaches, we find that the C-terminal region of DRC2 is critical for the coassembly of DRC2 and DRC1 to form the base plate of N-DRC and its attachment to the outer doublet microtubule. Loss of DRC2 in drc2 mutants disrupts the assembly of several other N-DRC subunits and also destabilizes the assembly of several closely associated structures such as the inner dynein arms, the radial spokes, and the calmodulin- and spoke-associated complex. Our study provides new insights into the range of ciliary defects that can lead to PCD.

PMID:
29167384
PMCID:
PMC5909927
DOI:
10.1091/mbc.E17-08-0510
[Indexed for MEDLINE]
Free PMC Article

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