Document Detail

Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases.
MedLine Citation:
PMID:  16902405     Owner:  NLM     Status:  MEDLINE    
The X-linked disorder oculocerebrorenal syndrome of Lowe is caused by mutation of the OCRL1 protein, an inositol polyphosphate 5-phosphatase. OCRL1 is localised to the Golgi apparatus and early endosomes, and can translocate to lamellipodia upon growth factor stimulation. We show here that OCRL1 interacts with several members of the rab family of small GTPases. Strongest interaction is seen with Golgi-associated rab1 and rab6 and endosomal rab5. Point mutants defective in rab binding fail to target to the Golgi apparatus and endosomes, strongly suggesting rab interaction is required for targeting of OCRL1 to these compartments. Membrane recruitment via rab binding is required for changes in Golgi and endosomal dynamics induced by overexpression of catalytically inactive OCRL1. In vitro experiments demonstrate that rab5 and rab6 directly stimulate the 5-phosphatase activity of OCRL1. We conclude that rabs play a dual role in regulation of OCRL1, firstly targeting it to the Golgi apparatus and endosomes, and secondly, directly stimulating the 5-phosphatase activity of OCRL1 after membrane recruitment.
Noora Hyvola; Aipo Diao; Eddie McKenzie; Alison Skippen; Shamshad Cockcroft; Martin Lowe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-10
Journal Detail:
Title:  The EMBO journal     Volume:  25     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-30     Completed Date:  2006-10-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  3750-61     Citation Subset:  IM    
Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester, UK.
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MeSH Terms
Amino Acid Sequence
Cell Compartmentation
Cell Line
Cell Membrane / metabolism*
Endosomes / metabolism
Enzyme Activation
Golgi Apparatus / physiology*
Molecular Sequence Data
Phosphoric Monoester Hydrolases / genetics,  metabolism*
Phosphotransferases (Alcohol Group Acceptor) / metabolism
Point Mutation
Protein Binding
Protein Transport
rab GTP-Binding Proteins / metabolism,  physiology*
rab1 GTP-Binding Proteins / metabolism
rab5 GTP-Binding Proteins / metabolism
Grant Support
068847/Z/02/A//Wellcome Trust
Reg. No./Substance:
0/Rab6 protein; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/phosphatidylinositol 4,5-biphosphate kinase; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC protein, human; EC 3.6.1.-/rab GTP-Binding Proteins; EC GTP-Binding Proteins; EC GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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