Conserved role of ATP synthase in mammalian cilia

Exp Cell Res. 2021 Apr 1;401(1):112520. doi: 10.1016/j.yexcr.2021.112520. Epub 2021 Feb 24.

Abstract

We previously found that ATP synthases localize to male-specific sensory cilia and control the ciliary response by regulating polycystin signalling in Caenorhabditis elegans. Herein, we discovered that the ciliary localization of ATP synthase is evolutionarily conserved in mammals. We showed that the ATP synthase subunit F1β is colocalized with the cilia marker acetylated α-tubulin in both mammalian renal epithelial cells (MDCK) and normal mouse cholangiocytes (NMCs). Treatment with ATP synthase inhibitor oligomycin impaired ciliogenesis in MDCK cells, and F1β was co-immunoprecipitated with PKD2 in mammalian cells. Our study provides evidence for the evolutionarily conserved localization of ATP synthase in cilia from worm to mammals. Defects in ATP synthase can lead to ciliary dysfunction, which may be a potential mechanism of polycystic kidney disease.

Keywords: ATP synthase; Cilia; Polycystin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Synthetase Complexes / chemistry
  • ATP Synthetase Complexes / genetics
  • Adenosine Triphosphate / genetics
  • Animals
  • Caenorhabditis elegans / genetics
  • Cilia / genetics*
  • Cilia / metabolism
  • Dogs
  • Kinesins / genetics
  • Madin Darby Canine Kidney Cells
  • Mammals
  • Mice
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Molecular Chaperones / genetics*
  • Oligomycins / pharmacology
  • Polycystic Kidney Diseases / enzymology
  • Polycystic Kidney Diseases / genetics
  • Polycystic Kidney Diseases / pathology
  • Protein Processing, Post-Translational / genetics
  • TRPP Cation Channels / genetics*

Substances

  • Atpaf2 protein, mouse
  • Molecular Chaperones
  • Oligomycins
  • TRPP Cation Channels
  • polycystic kidney disease 2 protein
  • Adenosine Triphosphate
  • ATP Synthetase Complexes
  • Mitochondrial Proton-Translocating ATPases
  • Kinesins