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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.

Original publication

DOI

10.15252/embr.201743903

Type

Journal article

Journal

EMBO Rep

Publication Date

10/2017

Volume

18

Pages

1817 - 1836

Keywords

Dictyostelium discoideum , macrophage, pathogen vacuole, phosphoinositide lipid, type IV secretion, A549 Cells, Dictyostelium, Endoplasmic Reticulum, GTP-Binding Proteins, Humans, Legionella pneumophila, Macrophages, Membrane Proteins, Nogo Proteins, Proteomics, Type IV Secretion Systems, Vacuoles