1. Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, Connecticut 06536, USA
2. Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, UMASS Medical School Two Biotech, 373 Plantation Street, Worcester, Massachusetts 01605, USA

Correspondence to: Craig R. Roy¹ Correspondence and requests for materials should be addressed to C.R.R. (Email: craig.roy@yale.edu).

Abstract

Rab1 is a GTPase that regulates the transport of endoplasmic-reticulum-derived vesicles in eukaryotic cells. The intracellular pathogen Legionella pneumophila subverts Rab1 function to create a vacuole that supports bacterial replication by a mechanism that is not well understood. Here we describe L. pneumophila proteins that control Rab1 activity directly. We show that a region in the DrrA (defect in Rab1 recruitment A) protein required for recruitment of Rab1 to membranes functions as a guanine nucleotide dissociation inhibitor displacement factor. A second region of the DrrA protein stimulated Rab1 activation by functioning as a guanine nucleotide exchange factor. The LepB protein was found to inactivate Rab1 by stimulating GTP hydrolysis, indicating that LepB has GTPase-activating protein activity that regulates removal of Rab proteins from membranes. Thus, L. pneumophila encodes proteins that regulate three distinct biochemical reactions critical for Rab GTPase membrane cycling to redirect Rab1 to the pathogen-occupied vacuole and to control Rab1 function.

1. Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, Connecticut 06536, USA
2. Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, UMASS Medical School Two Biotech, 373 Plantation Street, Worcester, Massachusetts 01605, USA

Correspondence to: Craig R. Roy¹ Correspondence and requests for materials should be addressed to C.R.R. (Email: craig.roy@yale.edu).

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