PtdIns-specific MPR pathway association of a novel WD40 repeat protein, WIPI49

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Authors

Colleges, School and Institutes

Abstract

WIPI49 is a member of a previously undescribed family of WD40-repeat proteins that we demonstrate binds 3-phosphorylated phosphoinositides. Immunofluorescent imaging indicates that WIPI49 is localized to both trans-Golgi and endosomal membranes, organelles between which it traffics in a microtubule-dependent manner. Live cell imaging establishes that WIPI49 traffics through the same set of endosomal membranes as that followed by the mannose-6-phosphate receptor (MPR), and consistent with this, WIPI49 is enriched in clathrin-coated vesicles. Ectopic expression of wild-type WIPI49 disrupts the proper functioning of this MPR pathway, whereas expression of a double point mutant (R221,222AWIP149) unable to bind phosphoinositides does not disrupt this pathway. Finally, suppression of WIP149 expression through RNAi, demonstrates that its presence is required for normal endosomal organization and distribution of the CI-MPR. We conclude that WIPI49 is a novel regulatory component of the endosomal and MPR pathway and that this role is dependent upon the PI-binding properties of its WD40 domain.

Bibliographic note

PtdIns-specific MPR Pathway Association of a Novel WD40 Repeat Protein, WIPI49, Tim R. Jeffries, Stephen K. Dove, Robert H. Michell, and Peter J. Parker, Molecular Biology of the Cell 2004 15:6, 2652-2663

Details

Original languageEnglish
Pages (from-to)2652-2663
Number of pages12
JournalMolecular Biology of the Cell
Volume15
Issue number6
Early online date19 Mar 2004
Publication statusPublished - 1 Jun 2004