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A Bifunctional Bacterial Protein Links GDI Displacement to Rab1 Activation
Matthias P. Machner1 and
Ralph R. Isberg1,2*
Rab guanosine triphosphatases (GTPases) regulate vesicle traffickingin eukaryotic cells by reversibly associating with lipid membranes.Inactive Rab GTPases are maintained in the cytosol by bindingto GDP-dissociation inhibitor (GDI). It is believed that specializedproteins are required to displace GDI from Rab GTPases beforeRab activation by guanosine diphosphate–guanosine 5'-triphosphate(GDP-GTP) exchange factors (GEFs). Here, we found that SidMfrom Legionella pneumophila could act as both GEF and GDI-displacementfactor (GDF) for Rab1. Rab1 released from GDI was inserted intoliposomal membranes and was used as a substrate for SidM-mediatednucleotide exchange. During host cell infection, recruitmentof Rab1 to Legionella-containing vacuoles depended on the GDFactivity of SidM. Thus, GDF and GEF activity can be promotedby a single protein, and GDF activity can coordinate Rab1 recruitmentfrom 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}tufts.edu
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