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 Wells, Robert N. Weinreb, Jeffrey Travers, Hemant Khanna, Yang Sun

Research output: Contribution to journalArticle

45 Citations (Scopus)

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
Article numberdds163
Pages (from-to)3333-3344
Number of pages12
JournalHuman Molecular Genetics
Volume21
Issue number15
DOIs
StatePublished - Aug 2012

Fingerprint

Oculocerebrorenal Syndrome
Cilia
phosphoinositide 5-phosphatase
Phenotype
Kidney
Mutation
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Retinal Pigments
Monomeric GTP-Binding Proteins
Zebrafish
Intellectual Disability
Glaucoma
Cataract
Embryonic Structures
Fibroblasts
Epithelial Cells
Maintenance
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Luo, N., West, C. C., Murga-Zamalloa, C. A., Sun, L., Anderson, R. M., Wells, C., ... 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

OCRL localizes to the primary cilium : A new role for cilia in Lowe syndrome. / Luo, Na; West, Callah C.; Murga-Zamalloa, Carlos A.; Sun, Lou; Anderson, Ryan M.; Wells, Clark; Weinreb, Robert N.; Travers, Jeffrey; Khanna, Hemant; Sun, Yang.

In: Human Molecular Genetics, Vol. 21, No. 15, dds163, 08.2012, p. 3333-3344.

Research output: Contribution to journalArticle

Luo, N, West, CC, Murga-Zamalloa, CA, Sun, L, Anderson, RM, Wells, C, Weinreb, RN, Travers, J, Khanna, H & Sun, Y 2012, 'OCRL localizes to the primary cilium: A new role for cilia in Lowe syndrome', Human Molecular Genetics, vol. 21, no. 15, dds163, pp. 3333-3344. https://doi.org/10.1093/hmg/dds163
Luo N, West CC, Murga-Zamalloa CA, Sun L, Anderson RM, Wells C et al. OCRL localizes to the primary cilium: A new role for cilia in Lowe syndrome. Human Molecular Genetics. 2012 Aug;21(15):3333-3344. dds163. https://doi.org/10.1093/hmg/dds163
Luo, Na ; West, Callah C. ; Murga-Zamalloa, Carlos A. ; Sun, Lou ; Anderson, Ryan M. ; Wells, Clark ; Weinreb, Robert N. ; Travers, Jeffrey ; Khanna, Hemant ; Sun, Yang. / OCRL localizes to the primary cilium : A new role for cilia in Lowe syndrome. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 15. pp. 3333-3344.
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