Sharafutdinov I, Knorr J, Soltan Esmaeili D, Backert S, Tegtmeyer-Backert N (2022)
Publication Language: English
Publication Type: Journal article
Publication year: 2022
Book Volume: 11
Article Number: 3
Journal Issue: 1
DOI: 10.3390/pathogens11010003
Cortactin is an actin-binding protein and actin-nucleation promoting factor regulating cytoskeletal rearrangements in eukaryotes. Helicobacter pylori is a gastric pathogen that exploits cortactin to its own benefit. During infection of gastric epithelial cells, H. pylori hijacks multiple cellular signaling pathways, leading to the disruption of key cell functions. Two bacterial virulence factors play important roles in this scenario, the vacuolating cytotoxin VacA and the translocated effector protein CagA of the cag type IV secretion system (T4SS). Specifically, by overruling the phosphorylation status of cortactin, H. pylori alternates the activity of molecular interaction partners of this important protein, thereby manipulating the performance of cytoskeletal rearrangements, endosomal trafficking and cell movement. Based on shRNA knockdown and other studies, it was previously reported that VacA utilizes cortactin for its cellular uptake, intracellular travel and induction of apoptosis by a mitochondria-dependent mechanism, while CagA induces cell scattering, motility and elongation. To investigate the role of cortactin in these phenotypes in more detail, we produced a complete knockout mutant of cortactin in the gastric adenocarcinoma cell line AGS by CRISPR-Cas9. These cells were infected with H. pylori wild-type or various isogenic mutant strains. Unexpectedly, cortactin deficiency did not prevent the uptake and formation of VacA-dependent vacuoles, nor the induction of apoptosis by internalized VacA, while the induction of T4SS-and CagA-dependent AGS cell movement and elongation were strongly reduced. Thus, we provide evidence that cortactin is required for the function of internalized CagA, but not VacA.
APA:
Sharafutdinov, I., Knorr, J., Soltan Esmaeili, D., Backert, S., & Tegtmeyer-Backert, N. (2022). Cortactin promotes effective ags cell scattering by helicobacter pylori caga, but not cellular vacuolization and apoptosis induced by the vacuolating cytotoxin vaca. Pathogens, 11(1). https://dx.doi.org/10.3390/pathogens11010003
MLA:
Sharafutdinov, Irshad, et al. "Cortactin promotes effective ags cell scattering by helicobacter pylori caga, but not cellular vacuolization and apoptosis induced by the vacuolating cytotoxin vaca." Pathogens 11.1 (2022).
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