Format

Send to

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

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

Author information

1
Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.
2
Center for Microscopy and Image Analysis, University of Zürich, Zürich, Switzerland.
3
Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
4
Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland hilbi@imm.uzh.ch.

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

PMID:
28835546
PMCID:
PMC5623866
DOI:
10.15252/embr.201743903
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center