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Science 318 (5852): 974-977

Copyright © 2007 by the American Association for the Advancement of Science

A Bifunctional Bacterial Protein Links GDI Displacement to Rab1 Activation

Matthias P. Machner1, and Ralph R. Isberg1,2*

Abstract: Rab guanosine triphosphatases (GTPases) regulate vesicle trafficking in eukaryotic cells by reversibly associating with lipid membranes. Inactive Rab GTPases are maintained in the cytosol by binding to GDP-dissociation inhibitor (GDI). It is believed that specialized proteins are required to displace GDI from Rab GTPases before Rab activation by guanosine diphosphate–guanosine 5'-triphosphate (GDP-GTP) exchange factors (GEFs). Here, we found that SidM from Legionella pneumophila could act as both GEF and GDI-displacement factor (GDF) for Rab1. Rab1 released from GDI was inserted into liposomal membranes and was used as a substrate for SidM-mediated nucleotide exchange. During host cell infection, recruitment of Rab1 to Legionella-containing vacuoles depended on the GDF activity of SidM. Thus, GDF and GEF activity can be promoted by a single protein, and GDF activity can coordinate Rab1 recruitment from the GDI-bound pool.

1 Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.
2 Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, MA 02111, USA.

* To whom correspondence should be addressed. E-mail: ralph.isberg{at}

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