Frontiers in Cellular and Infection Microbiology | |
SopB-Mediated Recruitment of SNX18 Facilitates Salmonella Typhimurium Internalization by the Host Cell | |
Barnett, Timothy C.1  Liebl, David2  Qi, Xiaying2  Zhe, Yang2  Teasdale, Rohan D.3  | |
[1] Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia;Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia;School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia | |
关键词: Salmonella; macropinocytosis; sorting nexin; phosphoinositide; host-pathogen interaction; | |
DOI : 10.3389/fcimb.2017.00257 | |
学科分类:生物科学(综合) | |
来源: Frontiers | |
【 摘 要 】
To invade epithelial cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) induces macropinocytosis through the action of virulence factors delivered across the host cell membrane via a type III secretion system. We show that after docking at the plasma membrane S. Typhimurium triggers rapid recruitment of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole. SNX18 recruitment required the inositol-phosphatase activity of the Salmonella effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation. SNX18 promotes formation of the SCV from the plasma membrane by acting as a scaffold to recruit Dynamin-2 and N-WASP in a process dependent on the SH3 domain of SNX18. Quantification of bacteria uptake revealed that overexpression of SNX18 increased bacteria internalization, whereas a decrease was detected in cells overexpressing the phosphoinositide-binding mutant R303Q, the ΔSH3 mutant, and in cells where endogenous levels of SNX18 were knocked-down. This study identifies SNX18 as a novel target of SopB and suggests a mechanism where S. Typhimurium engages host factors via local manipulation of phosphoinositide composition at the site of invasion to orchestrate the internalization process.
【 授权许可】
CC BY
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