Dataset Information

The Legionella protein VpdC is a ubiquitin-activated phospholipase effector

ABSTRACT: The goal of this project was to identify the host factor(s) required for allosteric activation of the phospholipase VpdC from the intracellular pathogen Legionella pneumophila. For that reason, we performed co-precipitation analyses from lysate of transiently transfected HEK293T cells producing either Red Fluorescent Protein (RFP)-tagged VpdC(257-884) or RFP-VpdC(257-610) as bait.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Legionella Pneumophila

TISSUE(S): Cell Culture, Kidney

SUBMITTER: David Anderson

LAB HEAD: Matthias Peter Machner

PROVIDER: PXD037059 | Pride | 2023-06-12

REPOSITORIES: Pride

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Publications

VpdC is a ubiquitin-activated phospholipase effector that regulates <i>Legionella</i> vacuole expansion during infection.

Li Xiao X Anderson D Eric DE Chang Yuen-Yan YY Jarnik Michal M Machner Matthias P MP

Proceedings of the National Academy of Sciences of the United States of America 20221121 48

Intravacuolar pathogens need to gradually expand their surrounding vacuole to accommodate the growing number of bacterial offspring during intracellular replication. Here we found that <i>Legionella pneumophila</i> controls vacuole expansion by fine-tuning the generation of lysophospholipids within the vacuolar membrane. Upon allosteric activation by binding to host ubiquitin, the type IVB (Dot/Icm) effector VpdC converts phospholipids into lysophospholipids which, at moderate concentrations, ar ...[more]

PMID: 36413498

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Project description:Carcinoma-associated fibroblasts (CAFs) that express ?-smooth-muscle-actin (?SMA+) contribute to cancer progression, but their precise origin and role in tumorigenesis is not established. Using mouse models of inflammation-induced gastric cancer, we show that at least 20% of CAFs originate from bone marrow and derive from mesenchymal stem cells (MSCs). Surprisingly, we find that ?SMA+ myofibroblasts (MF) are niche cells normally present in bone marrow and increase markedly in the bone marrow and blood during progression to dysplasia. MSC-derived CAFs that are recruited to the dysplastic stomach express IL-6, Wnt5? and BMP4 and show DNA hypomethylation. Bone marrow (BM)-derived CAFs strongly promote tumor growth in organotypic and xenograft models. In addition, CAFs are generated from MSCs and are recruited to distant tumor sites in a TGF-?- and SDF-1?-dependent manner. Carcinogenesis therefore involves the expansion and relocation of normal bone marrow niche cells to the tumor site where they create a new niche to sustain cancer progression. Since resident (non-BM-derived) CAFs could not be cultured and directly compared to BM-derived CAFs, we additionally isolated total RFP(+) gastric CAFs from aSMA-RFP mice with Helicobacter felis-induced dysplasia, and compared them to GFP(+) BM-derived gastric CAFs from mice with H. felis-induced dysplasia mice that had been transplanted with UBC-EGFP bone marrow. The RFP+ CAFs (HF CAF) represent total CAFs (of which only 20% were BM-derived), while the latter represented only BM-derived CAFs (BM CAF). We compared their gene expression using the Illumina array (MouseWG-6v2) directly after FACS sorting. Interestingly, the GFP+ BM-derived CAFs expressed higher levels of inflammatory genes (IL-6, IL-1?, IL-33) and a number of tumor and stem cell associated factors (CCL5, SPP1, Notch3, MMP9, CD47, CXCR4, PARP10,) compared to the total (RFP+) population of gastric CAFs. Comparison of bone marrow-derived GFP-labeled gastric CAFs versus all gastric CAFs.

Dataset Information

The Legionella protein VpdC is a ubiquitin-activated phospholipase effector

Publications

VpdC is a ubiquitin-activated phospholipase effector that regulates <i>Legionella</i> vacuole expansion during infection.

Similar Datasets

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