The Legionella pneumophila effector DrrA is sufficient to stimulate SNARE-dependent membrane fusion

Cell Host Microbe. 2012 Jan 19;11(1):46-57. doi: 10.1016/j.chom.2011.11.009.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / metabolism*
  • Cell Line
  • Endoplasmic Reticulum / metabolism
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Legionella pneumophila / pathogenicity*
  • Membrane Fusion*
  • Protein Binding
  • Qa-SNARE Proteins / metabolism*
  • R-SNARE Proteins / metabolism*
  • Vacuoles / metabolism
  • Vacuoles / microbiology
  • rab1 GTP-Binding Proteins / metabolism

Substances

  • Bacterial Proteins
  • Guanine Nucleotide Exchange Factors
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • Sec22B protein, human
  • SidM protein, Legionella pneumophila
  • rab1 GTP-Binding Proteins