Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases

Noora Hyvola, Aipo Diao, Eddie McKenzie, Alison Skippen, Shamshad Cockcroft, Martin Lowe

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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. ©2006 European Molecular Biology Organization.
    Original languageEnglish
    Pages (from-to)3750-3761
    Number of pages11
    JournalEMBO Journal
    Volume25
    Issue number16
    DOIs
    Publication statusPublished - 23 Aug 2006

    Keywords

    • Endosome
    • Golgi apparatus
    • OCRL1
    • Phosphoinositide
    • Rab

    Fingerprint

    Dive into the research topics of 'Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases'. Together they form a unique fingerprint.

    Cite this