Publikation: PIP5KIγ90 generated phosphatidylinositol-4,5-bisphosphate promotes uptake of Staphylococcus aureus by host cells
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Staphylococcus aureus, a gram-positive pathogen, invades cells mainly in an integrin-dependent manner. As the activity or conformation of several integrin-associated proteins can be regulated by phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2 ), we investigated the roles of PI-4,5-P2 and PI-4,5-P2 -producing enzymes in cellular invasion by S. aureus. PI-4,5-P2 accumulated upon contact of S. aureus with the host cell and targeting of an active PI-4,5-P2 phosphatase to the plasma membrane reduced bacterial invasion. Knockdown of individual phosphatidylinositol-4-phosphate 5-kinases revealed that phosphatidylinositol-4-phosphate 5-kinase γ (PIP5KIγ) plays an important role in bacterial internalization. Specific ablation of the talin and FAK binding motif in PIP5KIγ90 reduced bacterial invasion, which could be rescued by re-expression of an active, but not inactive PIP5KIγ90. Furthermore, PIP5KIγ90-deficient cells showed normal basal PI-4,5-P2 levels in the plasma membrane but reduced accumulation of PI-4,5-P2 and talin at sites of S. aureus attachment, and overall lower levels of FAK phosphorylation. These results highlight the importance of local synthesis of PI-4,5-P2 by a focal adhesion-associated lipid kinase for integrin-mediated internalization of S. aureus.
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SHI, Yong, Anne D. BERKING, Timo BAADE, Kyle R LEGATE, Reinhard FÄSSLER, Christof R. HAUCK, 2021. PIP5KIγ90 generated phosphatidylinositol-4,5-bisphosphate promotes uptake of Staphylococcus aureus by host cells. In: Molecular Microbiology. Wiley. 2021, 116(5), pp. 1249-1267. ISSN 0950-382X. eISSN 1365-2958. Available under: doi: 10.1111/mmi.14807BibTex
@article{Shi2021-11PIP5K-54969, year={2021}, doi={10.1111/mmi.14807}, title={PIP5KIγ90 generated phosphatidylinositol-4,5-bisphosphate promotes uptake of Staphylococcus aureus by host cells}, number={5}, volume={116}, issn={0950-382X}, journal={Molecular Microbiology}, pages={1249--1267}, author={Shi, Yong and Berking, Anne D. and Baade, Timo and Legate, Kyle R and Fässler, Reinhard and Hauck, Christof R.} }
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