title: OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome.
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.
authors.affiliation: Department of Ophthalmology, Glick Eye Institute, Indiana University, 1601 W Michigan St., Indianapolis, IN 46202, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Luo
authors.forename: Callah C
authors.initials: CC
authors.lastname: West
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Murga-Zamalloa
authors.forename: Lou
authors.initials: L
authors.lastname: Sun
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Anderson
authors.forename: Clark D
authors.initials: CD
authors.lastname: Wells
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Travers
authors.forename: Hemant
authors.initials: H
authors.lastname: Khanna
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D002923:Cilia / Q000737:chemistry / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism; D009154:Mutation; D009800:Oculocerebrorenal Syndrome / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
chemical_list: D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human