The cellular and physiological functions of the Lowe syndrome protein OCRL1.
Phosphoinositide lipids play a key role in cellular physiology, participating in a wide array of cellular processes. Consequently, mutation of phosphoinositide-metabolizing enzymes is responsible for a growing number of diseases in humans. Two related disorders, oculocerebrorenal syndrome of Lowe (OCRL) and Dent-2 disease, are caused by mutation of the inositol 5-phosphatase OCRL1. Here, we review recent advances in our understanding of OCRL1 function. OCRL1 appears to regulate many processes within the cell, most of which depend upon coordination of membrane dynamics with remodeling of the actin cytoskeleton. Recently developed animal models have managed to recapitulate features of Lowe syndrome and Dent-2 disease, and revealed new insights into the underlying mechanisms of these disorders. The continued use of both cell-based approaches and animal models will be key to fully unraveling OCRL1 function, how its loss leads to disease and, importantly, the development of therapeutics to treat patients.
Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK; Current address: Faculty of Medicine, Imperial College, London, UK.
Zenobia B
ZB
Mehta
Grzegorz
G
Pietka
Martin
M
Lowe
D000818:Animals; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics; D053040:Nephrolithiasis / Q000235:genetics / Q000378:metabolism; D009800:Oculocerebrorenal Syndrome / Q000235:genetics* / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism*
D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases
Dent disease; OCRL1; actin; ciliogenesis; endocytosis; inositol 5-phosphatase; oculocerebrorenal syndrome of Lowe; phagocytosis; phosphoinositide; zebrafish