Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe

Na Luo, Akhilesh Kumar, Michael Conwell, Robert N. Weinreb, Ryan Anderson, Yang Sun

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Inositol phosphatases are important regulators of cell signaling, polarity, and vesicular trafficking. Mutations in OCRL, an inositol polyphosphate 5-phosphatase, result in Oculocerebrorenal syndrome of Lowe, an X-linked recessive disorder that presents with congenital cataracts, glaucoma, renal dysfunction and mental retardation. INPP5B is a paralog of OCRL and shares similar structural domains. The roles of OCRL and INPP5B in the development of cataracts and glaucoma are not understood. Using ocular tissues, this study finds low levels of INPP5B present in human trabecular meshwork but high levels in murine trabecular meshwork. In contrast, OCRL is localized in the trabecular meshwork and Schlemm's canal endothelial cells in both human and murine eyes. In cultured human retinal pigmented epithelial cells, INPP5B was observed in the primary cilia. A functional role for INPP5B is revealed by defects in cilia formation in cells with silenced expression of INPP5B. This is further supported by the defective cilia formation in zebrafish Kupffer's vesicles and in cilia-dependent melanosome transport assays in inpp5b morphants. Taken together, this study indicates that OCRL and INPP5B are differentially expressed in the human and murine eyes, and play compensatory roles in cilia development.

Original languageEnglish
Article numbere66727
JournalPLoS One
Volume8
Issue number6
DOIs
StatePublished - Jun 21 2013

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Oculocerebrorenal Syndrome
Cell signaling
Polyphosphates
Cilia
Endothelial cells
cilia
Canals
Inositol
Phosphoric Monoester Hydrolases
Assays
Trabecular Meshwork
Tissue
Defects
glaucoma
cataract
eyes
Glaucoma
Cataract
mice
Melanosomes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe. / Luo, Na; Kumar, Akhilesh; Conwell, Michael; Weinreb, Robert N.; Anderson, Ryan; Sun, Yang.

In: PLoS One, Vol. 8, No. 6, e66727, 21.06.2013.

Research output: Contribution to journalArticle

Luo, Na ; Kumar, Akhilesh ; Conwell, Michael ; Weinreb, Robert N. ; Anderson, Ryan ; Sun, Yang. / Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe. In: PLoS One. 2013 ; Vol. 8, No. 6.
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