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| Subject Categories: Membranes & Transport | Molecular Biology of Disease |
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| The EMBO Journal
(2006) 25, 3750–3761, doi:10.1038/sj.emboj.7601274 Published online 10 August 2006 |
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| Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases |
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| Noora Hyvola1, Aipo Diao1, Eddie McKenzie1, Alison Skippen2, Shamshad Cockcroft2 and Martin Lowe1 |
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1 Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester, UK 2 Department of Physiology, University College London, London, UK To whom correspondence should be addressed Martin Lowe, Faculty of Life Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. Tel.: +44 161 275 5387; Fax: +44 161 275 1505; E-mail: martin.lowe@manchester.ac.uk Received 17 November 2005; Accepted 13 July 2006; Published online 10 August 2006. |
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| Abstract |
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| 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. |
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| Keywords: endosome, Golgi apparatus, OCRL1, phosphoinositide, rab |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSExtra Rabs unsnarl a lipid traffic jam Nature Medicine News and Views (01 Jul 2002) Nature Cell Biology News and Views (01 Jun 1999) RESEARCHThe EMBO Journal Article (01 Jun 2003) The EMBO Journal Article (01 Jun 2003) |
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