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Drug
Enzyme
Compound
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Query: UMLS:C0917816 (
mental retardation
)
15,867
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma,
mental retardation
, and proximal renal tubular dysfunction. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P
2
, cause Lowe syndrome. Previously we showed that OCRL localizes to the primary cilium, which has a distinct membrane phospholipid composition, but disruption of phosphoinositides in the ciliary membrane is poorly understood. Here, we demonstrate that cilia from Lowe syndrome patient fibroblasts exhibit increased levels of PI(4,5)P
2
and decreased levels of PI4P. In particular, subcellular distribution of PI(4,5)P
2
build-up was observed at the transition zone. Accumulation of ciliary PI(4,5)P
2
was pronounced in mouse embryonic fibroblasts (MEFs) derived from Lowe syndrome mouse model as well as in
Ocrl
-null MEFs, which was reversed by reintroduction of OCRL. Similarly, expression of wild-type OCRL reversed the elevated PI(4,5)P
2
in Lowe patient cells. Accumulation of
sonic hedgehog protein
in response to hedgehog agonist was decreased in MEFs derived from a Lowe syndrome mouse model. Together, our findings show for the first time an abnormality in ciliary phosphoinositides of both human and mouse cell models of Lowe syndrome.
...
PMID:Loss of OCRL increases ciliary PI(4,5)P
2
in Lowe oculocerebrorenal syndrome. 2887 Oct 46
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