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

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

Author information

1
Department of Ophthalmology, Glick Eye Institute, Indiana University, 1601 W Michigan St., Indianapolis, IN 46202, USA.

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 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.

PMID:
22543976
PMCID:
PMC3392109
DOI:
10.1093/hmg/dds163
[Indexed for MEDLINE]
Free PMC Article

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