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PMID: 22381590 Published · ppublish English Journal Article Review

Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL.

Trends in biochemical sciences ·Vol. 37 ·No. 4 ·2012-04-00 ·Pages 134-43

Pirruccello M, De Camilli P

Abstract

The precise regulation of phosphoinositide lipids in cellular membranes is crucial for cellular survival and function. Inositol 5-phosphatases have been implicated in a variety of disorders, including various cancers, obesity, type 2 diabetes, neurodegenerative diseases and rare genetic conditions. Despite the obvious impact on human health, relatively little structural and biochemical information is available for this family. Here, we review recent structural and mechanistic work on the 5-phosphatases with a focus on OCRL, whose loss of function results in oculocerebrorenal syndrome of Lowe and Dent 2 disease. Studies of OCRL emphasize how the actions of 5-phosphatases rely on both intrinsic and extrinsic membrane recognition properties for full catalytic function. Additionally, structural analysis of missense mutations in the catalytic domain of OCRL provides insight into the phenotypic heterogeneity observed in Lowe syndrome and Dent disease.

MeSH Terms
Animals Dent Disease/genetics,metabolism Humans Inositol Polyphosphate 5-Phosphatases Oculocerebrorenal Syndrome/genetics,metabolism Phosphoric Monoester Hydrolases/chemistry,genetics,metabolism
Chemicals
Phosphoric Monoester Hydrolases OCRL protein, human Inositol Polyphosphate 5-Phosphatases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pirruccello Michelle
Department of Cell Biology, HHMI and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510, USA.
De Camilli Pietro
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Article Info
Journal
Trends in biochemical sciences
Abbr.
Trends Biochem Sci
ISSN
0968-0004
DOI
10.1016/j.tibs.2012.01.002
Published
2012-04-00
Epub
2012-00-28
Pages
134-43
Language
English
Region
England
NLM ID
7610674
PMCID
PMC3323734
Subset
IM
Grants
NIDDK NIH HHS · R01 DK082700-03 · United States
NIDA NIH HHS · P30 DA018343 · United States
NIDDK NIH HHS · R01 DK082700 · United States
NINDS NIH HHS · R37 NS036251 · United States
NINDS NIH HHS · R37 NS036251-15 · United States
External Links
PubMed source DOI: 10.1016/j.tibs.2012.01.002 PMC Full Text View journal details
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