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Yip3 catalyses the dissociation of endosomal Rab–GDI complexes

Abstract

Human cells contain more than 60 small G proteins of the Rab family, which are localized to the surfaces of distinct membrane compartments and regulate transport vesicle formation, motility, docking and fusion1,2,3. Prenylated Rabs also occur in the cytosol bound to GDI4,5 (guanine nucleotide dissociation inhibitor), which binds to Rabs in their inactive state. Prenyl Rab–GDI complexes contain all of the information necessary to direct Rab delivery onto distinct membrane compartments6,7,8. The late endosomal, prenyl Rab9 binds GDI with very high affinity9, which led us to propose that there might be a ‘GDI-displacement factor’ to catalyse dissociation of Rab–GDI complexes and to enable transfer of Rabs from GDI onto membranes6,10. Indeed, we have previously shown that endosomal membranes contain a proteinaceous factor that can act in this manner10. Here we show that the integral membrane protein, Yip3, acts catalytically to dissociate complexes of endosomal Rabs bound to GDI, and to deliver them onto membranes. We propose that the conserved Yip proteins serve as GDI-displacement factors for the targeting of Rab GTPases in eukaryotic cells.

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Figure 1: Yip3 dissociates Rab9–GDI complexes catalytically.
Figure 2: Human Yip3 catalyses the physical displacement of Rab9 from GDI, as determined by gel filtration chromatography.
Figure 3: Yip3-catalysed membrane recruitment is specific for endosomal Rabs in vitro and in vivo.

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Acknowledgements

We thank F. Barr and T. Meyer for providing Rab2 and Rab1A plasmids, respectively, and B. Stafford and C. Melton for technical assistance. This work was supported by grants from the NIH and the American Heart Association. U.S. and D.A. were postdoctoral fellows of the Swedish Foundation for International Cooperation in Research and Higher Education and the Leukemia and Lymphoma Society, respectively.

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Correspondence to Suzanne R. Pfeffer.

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Sivars, U., Aivazian, D. & Pfeffer, S. Yip3 catalyses the dissociation of endosomal Rab–GDI complexes. Nature 425, 856–859 (2003). https://doi.org/10.1038/nature02057

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