ZFIN ID: ZDB-PUB-120503-10
OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome
Luo, N., West, C., Murga-Zamalloa, C., Sun, L., Anderson, R.M., Wells, C., Weinreb, R.N., Travers, J.B., Khanna, H., and Sun, Y.
Date: 2012
Source: Human molecular genetics   21(15): 3333-3344 (Journal)
Registered Authors: Anderson, Ryan, Khanna, Hemant
Keywords: none
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
PubMed: 22543976 Full text @ Hum. Mol. Genet.
FIGURES
ABSTRACT

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 wildtype 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.

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