ER remodeling by the large GTPase atlastin promotes vacuolar growth of Legionella pneumophila

EMBO Rep. 2017 Oct;18(10):1817-1836. doi: 10.15252/embr.201743903. Epub 2017 Aug 23.

Abstract

The pathogenic bacterium Legionella pneumophila replicates in host cells within a distinct ER-associated compartment termed the Legionella-containing vacuole (LCV). How the dynamic ER network contributes to pathogen proliferation within the nascent LCV remains elusive. A proteomic analysis of purified LCVs identified the ER tubule-resident large GTPase atlastin3 (Atl3, yeast Sey1p) and the reticulon protein Rtn4 as conserved LCV host components. Here, we report that Sey1/Atl3 and Rtn4 localize to early LCVs and are critical for pathogen vacuole formation. Sey1 overproduction promotes intracellular growth of L. pneumophila, whereas a catalytically inactive, dominant-negative GTPase mutant protein, or Atl3 depletion, restricts pathogen replication and impairs LCV maturation. Sey1 is not required for initial recruitment of ER to PtdIns(4)P-positive LCVs but for subsequent pathogen vacuole expansion. GTP (but not GDP) catalyzes the Sey1-dependent aggregation of purified, ER-positive LCVs in vitro Thus, Sey1/Atl3-dependent ER remodeling contributes to LCV maturation and intracellular replication of L. pneumophila.

Keywords: Dictyostelium discoideum; macrophage; pathogen vacuole; phosphoinositide lipid; type IV secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Dictyostelium / microbiology
  • Endoplasmic Reticulum / microbiology
  • Endoplasmic Reticulum / physiology*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Legionella pneumophila / growth & development*
  • Legionella pneumophila / pathogenicity
  • Macrophages / microbiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nogo Proteins / genetics
  • Nogo Proteins / metabolism
  • Proteomics
  • Type IV Secretion Systems
  • Vacuoles / metabolism*
  • Vacuoles / microbiology*

Substances

  • Membrane Proteins
  • Nogo Proteins
  • RTN4 protein, human
  • Type IV Secretion Systems
  • ATL1 protein, human
  • GTP-Binding Proteins