title: Structure and function of the Lowe syndrome protein OCRL1.
abstract: Oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder with the hallmark features of congenital cataracts, mental retardation and Fanconi syndrome of the kidney proximal tubules. OCRL was first described in 1952, and exactly four decades later, the gene responsible was identified and found to encode a protein highly homologous to inositol polyphosphate 5-phosphatase. This suggested that Lowe syndrome may represent an inborn error of inositol phosphate metabolism, and subsequent studies confirmed that such metabolism is indeed perturbed in Lowe syndrome cells. However, the mechanism by which loss of function of the OCRL1 protein brings about Lowe syndrome remains ill defined. In this review, I will discuss our understanding of OCRL1, including where it is localized, what it interacts with and what its possible functions might be. I will then discuss possible mechanisms by which loss of OCRL1 may bring about cellular defects that manifest themselves in the pathology of Lowe syndrome.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. martin.lowe@manchester.ac.uk
authors.forename: Martin
authors.initials: M
authors.lastname: Lowe
mesh_terms: D000199:Actins / Q000378:metabolism; D017398:Alternative Splicing; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009800:Oculocerebrorenal Syndrome / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020744:rac GTP-Binding Proteins / Q000737:chemistry
chemical_list: D000199:Actins; D008565:Membrane Proteins; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human; D020744:rac GTP-Binding Proteins