Legionella- and host-driven lipid flux at LCV-ER membrane contact sites promotes vacuole remodeling

被引：13

作者：

Vormittag, Simone ^{[1
]}

Huesler, Dario ^{[1
]}

Haneburger, Ina ^{[1
]}

Kroniger, Tobias ^{[2
]}

Anand, Aby ^{[3
,4
]}

Prantl, Manuel ^{[1
]}

Barisch, Caroline ^{[3
,4
]}

Maass, Sandra ^{[2
]}

Becher, Doerte ^{[2
]}

Letourneur, Francois ^{[5
]}

Hilbi, Hubert ^{[1
]}

机构：

[1] Univ Zurich, Inst Med Microbiol, Zurich, Switzerland

[2] Univ Greifswald, Inst Microbiol, Greifswald, Germany

[3] Univ Osnabruck, Div Mol Infect Biol, Osnabruck, Germany

[4] Univ Osnabruck, Ctr Cellular Nanoanalyt, Osnabruck, Germany

[5] Univ Montpellier, INSERM, CNRS, Lab Pathogen Host Interact, Montpellier, France

来源：

EMBO REPORTS | 2023年 / 24卷 / 03期

基金：

瑞士国家科学基金会;

关键词：

Atlastin; Dictyostelium discoideum; Legionnaires' disease; oxysterol binding protein; Sac1 phosphoinositide phosphatase; EFFECTOR PROTEIN DRRA; RAB GTPASE FUNCTION; ENDOPLASMIC-RETICULUM; PHOSPHATIDYLINOSITOL; 4-PHOSPHATE; NUCLEOTIDE-EXCHANGE; RETROGRADE TRAFFICKING; DICTYOSTELIUM NRAMP1; GDI DISPLACEMENT; PATHOGEN VACUOLE; STRUCTURAL BASIS;

D O I：

10.15252/embr.202256007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Legionella pneumophila replicates in macrophages and amoeba within a unique compartment, the Legionella-containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide lipid conversion from PtdIns(3)P to PtdIns(4)P, fusion with ER-derived vesicles and a tight association with the ER. Proteomics of purified LCVs indicate the presence of membrane contact sites (MCS) proteins possibly implicated in lipid exchange. Using dually fluorescence-labeled Dictyostelium discoideum amoeba, we reveal that VAMP-associated protein (Vap) and the PtdIns(4)P 4-phosphatase Sac1 localize to the ER, and Vap also localizes to the LCV membrane. Furthermore, Vap as well as Sac1 promote intracellular replication of L. pneumophila and LCV remodeling. Oxysterol binding proteins (OSBPs) preferentially localize to the ER (OSBP8) or the LCV membrane (OSBP11), respectively, and restrict (OSBP8) or promote (OSBP11) bacterial replication and LCV expansion. The sterol probes GFP-D4H* and filipin indicate that sterols are rapidly depleted from LCVs, while PtdIns(4)P accumulates. In addition to Sac1, the PtdIns(4)P-subverting L. pneumophila effector proteins LepB and SidC also support LCV remodeling. Taken together, the Legionella- and host cell-driven PtdIns(4)P gradient at LCV-ER MCSs promotes Vap-, OSBP- and Sac1-dependent pathogen vacuole maturation.

引用

页数：20