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

Raqual Bower, Douglas Tritschler, Kristyn VanderWaal Mills, Thomas Heuser, Daniela Nicastro, Mary E. Portera

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)137-153
Number of pages17
JournalMolecular biology of the cell
Volume29
Issue number2
DOIs
StatePublished - Jan 15 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'DRC2/CCDC65 is a central hub for assembly of the nexin–dynein regulatory complex and other regulators of ciliary and flagellar motility'. Together they form a unique fingerprint.

  • Cite this