Linked Life Data

12915445

Source:http://linkedlifedata.com/resource/pubmed/id/12915445

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2003-9-16
pubmed:abstractText
The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked disorder characterized by severe mental retardation, congenital cataracts and renal Fanconi syndrome. OCRL1 protein is a phosphatidylinositol 4,5-bisphosphate 5-phosphatase with a C-terminal RhoGAP domain. Considering the pleiotropic cellular functions of Rho GTPases (Rho, Rac and Cdc42) and their dysregulation in several forms of mental retardation, we have investigated the so far unexplored function of the RhoGAP domain of OCRL1. Activated Rac GTPase was found to stably associate with the OCRL1 RhoGAP domain in vitro and to co-immunoprecipitate with endogenous OCRL1. Contrasting with other GAPs, OCRL1 RhoGAP exhibited a significant interaction with GDP bound Rac in vitro. As compared to Rac, other Rho GTPases tested showed reduced (Cdc42) or no binding (RhoA, RhoG) to OCRL1 RhoGAP. Immunofluorescence studies in HEK and COS7 cells and Golgi perturbation assays with Brefeldin A demonstrated that a fraction of endogenous Rac co-localizes with OCRL1 and gamma-adaptin in the trans-Golgi network. The OCRL1 RhoGAP domain showed low Rac GAP activity in vitro, and when expressed in Swiss 3T3 cells induced specific inhibition of RacGTP dependent ruffles, consistent with OCRL1 being an active RacGAP. OCRL1 appears to be a bifunctional protein which, in addition to its PIP2 5-phosphatase activity, binds to Rac GTPase. This novel property may play a role in localizing OCRL1 to the trans-Golgi network. Moreover, loss of OCRL1 RhoGAP and the resulting alteration in Rho pathways may contribute to mental retardation in Lowe syndrome, as illustrated in other forms of X-linked mental retardation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2449-56
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12915445-Adaptor Protein Complex gamma Subunits, pubmed-meshheading:12915445-Animals, pubmed-meshheading:12915445-Brefeldin A, pubmed-meshheading:12915445-COS Cells, pubmed-meshheading:12915445-Cells, Cultured, pubmed-meshheading:12915445-Cercopithecus aethiops, pubmed-meshheading:12915445-Enzyme Activation, pubmed-meshheading:12915445-HeLa Cells, pubmed-meshheading:12915445-Humans, pubmed-meshheading:12915445-Mice, pubmed-meshheading:12915445-Oculocerebrorenal Syndrome, pubmed-meshheading:12915445-Phosphoric Monoester Hydrolases, pubmed-meshheading:12915445-Precipitin Tests, pubmed-meshheading:12915445-Protein Structure, Tertiary, pubmed-meshheading:12915445-Protein Synthesis Inhibitors, pubmed-meshheading:12915445-Proteins, pubmed-meshheading:12915445-Swiss 3T3 Cells, pubmed-meshheading:12915445-X Chromosome, pubmed-meshheading:12915445-rho GTP-Binding Proteins, pubmed-meshheading:12915445-trans-Golgi Network
pubmed:year
2003
pubmed:articleTitle
Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network.
pubmed:affiliation
Institut Cochin, Département de Génétiques, Développement et Pathologie Moléculaire, INSERM U567/CNRS UMR8104/Université Paris V, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't