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

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.

Citation

Na Luo, Callah C West, Carlos A Murga-Zamalloa, Lou Sun, Ryan M Anderson, Clark D Wells, Robert N Weinreb, Jeffrey B Travers, Hemant Khanna, Yang Sun. OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Human molecular genetics. 2012 Aug 01;21(15):3333-44

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PMID: 22543976

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