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

作者：Steiner Bernhard; Swart Anna Leoni; Welin Amanda; Weber Stephen; Personnic Nicolas; Kaech Andres; Freyre Christophe; Ziegler Urs; Klemm Robin W; Hilbi Hubert^*

来源：EMBO Reports, 2017, 18(10): 1817-1836.

DOI：10.15252/embr.201743903

• Dictyostelium discoideum
• macrophage
• pathogen vacuole
• phosphoinositide lipid
• type IV secretion

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.

• 出版日期2017-10
• 单位河北医科大学