OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome

Hum Mol Genet. 2012 Aug 1;21(15):3333-44. doi: 10.1093/hmg/dds163. Epub 2012 Apr 27.


Oculocerebral renal syndrome of Lowe (OCRL or Lowe syndrome), a severe X-linked congenital disorder characterized by congenital cataracts and glaucoma, mental retardation and kidney dysfunction, is caused by mutations in the OCRL gene. OCRL is a phosphoinositide 5-phosphatase that interacts with small GTPases and is involved in intracellular trafficking. Despite extensive studies, it is unclear how OCRL mutations result in a myriad of phenotypes found in Lowe syndrome. Our results show that OCRL localizes to the primary cilium of retinal pigment epithelial cells, fibroblasts and kidney tubular cells. Lowe syndrome-associated mutations in OCRL result in shortened cilia and this phenotype can be rescued by the introduction of wild-type OCRL; in vivo, knockdown of ocrl in zebrafish embryos results in defective cilia formation in Kupffer vesicles and cilia-dependent phenotypes. Cumulatively, our data provide evidence for a role of OCRL in cilia maintenance and suggest the involvement of ciliary dysfunction in the manifestation of Lowe syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cilia / chemistry
  • Cilia / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Fibroblasts / metabolism
  • Genotype
  • Humans
  • Immunohistochemistry
  • Kidney Tubules / metabolism
  • Mutation
  • Oculocerebrorenal Syndrome / genetics
  • Oculocerebrorenal Syndrome / metabolism*
  • Phosphoric Monoester Hydrolases / analysis*
  • Phosphoric Monoester Hydrolases / genetics*
  • Phosphoric Monoester Hydrolases / metabolism
  • Transfection
  • Zebrafish / embryology
  • Zebrafish / metabolism


  • Phosphoric Monoester Hydrolases
  • OCRL protein, human