c21orf59/kurly Controls Both Cilia Motility and Polarization

Cell Rep. 2016 Mar 1;14(8):1841-9. doi: 10.1016/j.celrep.2016.01.069. Epub 2016 Feb 18.

Abstract

Cilia are microtubule-based projections that function in the movement of extracellular fluid. This requires cilia to be: (1) motile and driven by dynein complexes and (2) correctly polarized on the surface of cells, which requires planar cell polarity (PCP). Few factors that regulate both processes have been discovered. We reveal that C21orf59/Kurly (Kur), a cytoplasmic protein with some enrichment at the base of cilia, is needed for motility; zebrafish mutants exhibit characteristic developmental abnormalities and dynein arm defects. kur was also required for proper cilia polarization in the zebrafish kidney and the larval skin of Xenopus laevis. CRISPR/Cas9 coupled with homologous recombination to disrupt the endogenous kur locus in Xenopus resulted in the asymmetric localization of the PCP protein Prickle2 being lost in mutant multiciliated cells. Kur also makes interactions with other PCP components, including Disheveled. This supports a model wherein Kur plays a dual role in cilia motility and polarization.

Keywords: Kurly (Kur); c21orf59; cilia; ciliopathy; disheveled; multiciliated cell; planar cell polarity; primary ciliary dyskinesia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • CRISPR-Cas Systems
  • Cell Movement
  • Cell Polarity
  • Cilia / metabolism
  • Dishevelled Proteins / genetics
  • Dishevelled Proteins / metabolism
  • Embryo, Nonmammalian
  • Gene Expression
  • Genetic Loci
  • Homologous Recombination
  • Kidney / cytology
  • Kidney / growth & development
  • Kidney / metabolism
  • LIM Domain Proteins / genetics*
  • LIM Domain Proteins / metabolism
  • Larva / genetics
  • Larva / growth & development
  • Larva / metabolism
  • Membrane Proteins
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Mutation
  • Protein Binding
  • Signal Transduction
  • Skin / cytology
  • Skin / growth & development
  • Skin / metabolism
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics*
  • Xenopus laevis / metabolism
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • DVL1 protein, Xenopus
  • Dishevelled Proteins
  • Dvl2 protein, zebrafish
  • LIM Domain Proteins
  • Membrane Proteins
  • Xenopus Proteins
  • Zebrafish Proteins