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

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

Research output: Contribution to journalArticle

55 Scopus citations

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.

Original languageEnglish (US)
Article numberdds163
Pages (from-to)3333-3344
Number of pages12
JournalHuman molecular genetics
Volume21
Issue number15
DOIs
StatePublished - Aug 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'OCRL localizes to the primary cilium: A new role for cilia in Lowe syndrome'. Together they form a unique fingerprint.

  • Cite this

    Luo, N., West, C. C., Murga-Zamalloa, C. A., Sun, L., Anderson, R. M., Wells, C. D., Weinreb, R. N., Travers, J. B., Khanna, H., & Sun, Y. (2012). OCRL localizes to the primary cilium: A new role for cilia in Lowe syndrome. Human molecular genetics, 21(15), 3333-3344. [dds163]. https://doi.org/10.1093/hmg/dds163