Targeted deletion of the AAA-ATPase Ruvbl1 in mice disrupts ciliary integrity and causes renal disease and hydrocephalus

Exp Mol Med. 2018 Jun 28;50(6):1-17. doi: 10.1038/s12276-018-0108-z.

Abstract

Ciliopathies comprise a large number of hereditary human diseases and syndromes caused by mutations resulting in dysfunction of either primary or motile cilia. Both types of cilia share a similar architecture. While primary cilia are present on most cell types, expression of motile cilia is limited to specialized tissues utilizing ciliary motility. We characterized protein complexes of ciliopathy proteins and identified the conserved AAA-ATPase Ruvbl1 as a common novel component. Here, we demonstrate that Ruvbl1 is crucial for the development and maintenance of renal tubular epithelium in mice: both constitutive and inducible deletion in tubular epithelial cells result in renal failure with tubular dilatations and fewer ciliated cells. Moreover, inducible deletion of Ruvbl1 in cells carrying motile cilia results in hydrocephalus, suggesting functional relevance in both primary and motile cilia. Cilia of Ruvbl1-negative cells lack crucial proteins, consistent with the concept of Ruvbl1-dependent cytoplasmic pre-assembly of ciliary protein complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / deficiency*
  • Animals
  • Cilia / genetics
  • Cilia / metabolism
  • Ciliopathies* / genetics
  • Ciliopathies* / metabolism
  • Ciliopathies* / pathology
  • DNA Helicases / deficiency*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Deletion*
  • Hydrocephalus* / genetics
  • Hydrocephalus* / metabolism
  • Hydrocephalus* / pathology
  • Kidney Diseases* / genetics
  • Kidney Diseases* / metabolism
  • Kidney Diseases* / pathology
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Mice
  • Mice, Transgenic

Substances

  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, mouse