OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome
- Authors
- 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.
- ID
- ZDB-PUB-120503-10
- 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.
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.