title: The Legionella pneumophila effector DrrA is sufficient to stimulate SNARE-dependent membrane fusion.
abstract: The intracellular bacterial pathogen Legionella pneumophila subverts host membrane transport pathways to promote fusion of vesicles exiting the endoplasmic reticulum (ER) with the pathogen-containing vacuole. During infection there is noncanonical pairing of the SNARE protein Sec22b on ER-derived vesicles with plasma membrane (PM)-localized syntaxin proteins on the vacuole. We show that the L. pneumophila Rab1-targeting effector DrrA is sufficient to stimulate this noncanonical SNARE association and promote membrane fusion. DrrA activation of the Rab1 GTPase on PM-derived organelles stimulated the tethering of ER-derived vesicles with the PM-derived organelle, resulting in vesicle fusion through the pairing of Sec22b with the PM syntaxin proteins. Thus, the effector protein DrrA stimulates a host membrane transport pathway that enables ER-derived vesicles to remodel a PM-derived organelle, suggesting that Rab1 activation at the PM is sufficient to promote the recruitment and fusion of ER-derived vesicles.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06526, USA.
authors.forename: Kohei
authors.initials: K
authors.lastname: Arasaki
authors.forename: Derek K
authors.initials: DK
authors.lastname: Toomre
authors.forename: Craig R
authors.initials: CR
authors.lastname: Roy
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D016952:Legionella pneumophila / Q000472:pathogenicity*; D008561:Membrane Fusion; D011485:Protein Binding; D050765:Qa-SNARE Proteins / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; C572028:Sec22B protein, human; C539733:SidM protein, Legionella pneumophila; D020761:rab1 GTP-Binding Proteins