SopB-Mediated Recruitment of SNX18 Facilitates Salmonella Typhimurium Internalization by the Host Cell

Liebl, David; Qi, Xiaying; Yang, Zhe; Barnett, Timothy C.; Teasdale, Rohan D.

doi:10.3389/fcimb.2017.00257

Cited by 31 publications

(27 citation statements)

References 64 publications

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“…We found that TMEM170B mainly colocalized on the cell membrane (Fig. 2c ), which was labeled by the Na,K-ATPase (alpha 1) as shown previously 22 . A similar observation (Supplementary Fig.…”

Section: Resultssupporting

confidence: 88%

Transmembrane protein 170B is a novel breast tumorigenesis suppressor gene that inhibits the Wnt/β-catenin pathway

Han

Zhou

et al. 2018

Cell Death Dis

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The identification of specific drug targets guides the development of precise cancer treatments. Compared with oncogenes, tumor suppressor genes have been poorly studied in the treatment of breast cancer. We integrate the microRNA expression array from GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) databases in clinical breast cancer tissues, and find that miR-27a is significantly upregulated and correlated with poor survival outcome and tumor progression. Transmembrane protein 170B (TMEM170B), a new functional target of miR-27a, is identified via target prediction and experimental validation, suppressing breast cancer proliferation, metastasis, and tumorigenesis. Furthermore, TMEM170B overexpression promotes cytoplasmic β-catenin phosphorylation, resulting in the inhibition of β-catenin stabilization, reduction of nuclear β-catenin levels and downstream targets expression. Clinically, TMEM170B or β-catenin expression is significantly correlated with overall survival ratio in breast cancer patients. Thus, these results highlight TMEM170B as a novel tumor suppressor target in association with the β-catenin pathway, which may provide a new therapeutic approach for human breast cancer therapy.

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Section: Resultssupporting

confidence: 88%

Transmembrane protein 170B is a novel breast tumorigenesis suppressor gene that inhibits the Wnt/β-catenin pathway

Han

Zhou

et al. 2018

Cell Death Dis

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“…These phosphoinositides recruit and activate AKT through its PH domain, thereby promoting host cell survival following infection 202,203 . In the same manner described for endogenous endocytosis, the 3-phosphorylated inositides produced by SopB support the recruitment of the PX-BAR domain-containing proteins SNX9 180 and SNX18 204 , likely facilitating dynaminmediated scission of the SCV from the PM.…”

Section: Figure 2 Bacterial Effectors Alter Early Endocytic Traffic By Subverting Phosphoinositide Metabolism (A)mentioning

confidence: 75%

Endocytosis and the internalization of pathogenic organisms: focus on phosphoinositides

Walpole

Grinstein

2020

F1000Res

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Despite their comparatively low abundance in biological membranes, phosphoinositides are key to the regulation of a diverse array of signaling pathways and direct membrane traffic. The role of phosphoinositides in the initiation and progression of endocytic pathways has been studied in considerable depth. Recent advances have revealed that distinct phosphoinositide species feature prominently in clathrin-dependent and -independent endocytosis as well as in phagocytosis and macropinocytosis. Moreover, a variety of intracellular and cell-associated pathogens have developed strategies to commandeer host cell phosphoinositide metabolism to gain entry and/or metabolic advantage, thereby promoting their survival and proliferation. Here, we briefly survey the current knowledge on the involvement of phosphoinositides in endocytosis, phagocytosis, and macropinocytosis and highlight several examples of molecular mimicry employed by pathogens to either “hitch a ride” on endocytic pathways endogenous to the host or create an entry path of their own.

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“…(Fig 6A). SopB and IpgD both control the phosphoinositide composition of the vacuole membrane and might modulate bacteria-containing vacuole rupture in a similar macropinosome-dependent manner, perhaps via the recruitment of Rab11 [79,117] or sorting nexins [97,118–120].…”

Section: Discussionmentioning

confidence: 99%

SopF, a phosphoinositide binding effector, promotes the stability of the nascent Salmonella-containing vacuole

et al. 2019

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The enteric bacterial pathogen Salmonella enterica serovar Typhimurium ( S . Typhimurium), utilizes two type III secretion systems (T3SSs) to invade host cells, survive and replicate intracellularly. T3SS1 and its dedicated effector proteins are required for bacterial entry into non-phagocytic cells and establishment and trafficking of the nascent Salmonella -containing vacuole (SCV). Here we identify the first T3SS1 effector required to maintain the integrity of the nascent SCV as SopF. SopF associates with host cell membranes, either when translocated by bacteria or ectopically expressed. Recombinant SopF binds to multiple phosphoinositides in protein-lipid overlays, suggesting that it targets eukaryotic cell membranes via phospholipid interactions. In yeast, the subcellular localization of SopF is dependent on the activity of Mss4, a phosphatidylinositol 4-phosphate 5-kinase that generates PI(4,5)P 2 from PI(4)P, indicating that membrane recruitment of SopF requires specific phospholipids. Ectopically expressed SopF partially colocalizes with specific phosphoinositide pools present on the plasma membrane in mammalian cells and with cytoskeletal-associated markers at the leading edge of cells. Translocated SopF concentrates on plasma membrane ruffles and around intracellular bacteria, presumably on the SCV. SopF is not required for bacterial invasion of non-phagocytic cells but is required for maintenance of the internalization vacuole membrane as infection with a S . Typhimurium Δ sopF mutant led to increased lysis of the SCV compared to wild type bacteria. Our structure-function analysis shows that the carboxy-terminal seven amino acids of SopF are essential for its membrane association in host cells and to promote SCV membrane stability. We also describe that SopF and another T3SS1 effector, SopB, act antagonistically to modulate nascent SCV membrane dynamics. In summary, our study highlights that a delicate balance of type III effector activities regulates the stability of the Salmonella internalization vacuole.

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SopB-Mediated Recruitment of SNX18 Facilitates Salmonella Typhimurium Internalization by the Host Cell

Cited by 31 publications

References 64 publications

Transmembrane protein 170B is a novel breast tumorigenesis suppressor gene that inhibits the Wnt/β-catenin pathway

Transmembrane protein 170B is a novel breast tumorigenesis suppressor gene that inhibits the Wnt/β-catenin pathway

Endocytosis and the internalization of pathogenic organisms: focus on phosphoinositides

SopF, a phosphoinositide binding effector, promotes the stability of the nascent Salmonella-containing vacuole

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