SIK2 orchestrates actin-dependent host response upon Salmonella infection.

Salmonella is an intracellular pathogen of a substantial global health concern. In order to identify key players involved in Salmonella infection, we performed a global host phosphoproteome analysis subsequent to bacterial infection. Thereby, we identified the kinase SIK2 as a central component of the host defense machinery upon Salmonella infection. ...
SIK2 depletion favors the escape of bacteria from the Salmonella-containing vacuole (SCV) and impairs Xenophagy, resulting in a hyperproliferative phenotype. Mechanistically, SIK2 associates with actin filaments under basal conditions; however, during bacterial infection, SIK2 is recruited to the SCV together with the elements of the actin polymerization machinery (Arp2/3 complex and Formins). Notably, SIK2 depletion results in a severe pathological cellular actin nucleation and polymerization defect upon Salmonella infection. We propose that SIK2 controls the formation of a protective SCV actin shield shortly after invasion and orchestrates the actin cytoskeleton architecture in its entirety to control an acute Salmonella infection after bacterial invasion.
Mesh Terms:
Actins, Animals, Cells, Cultured, Epithelial Cells, HCT116 Cells, HEK293 Cells, HeLa Cells, Host-Pathogen Interactions, Humans, Immunoblotting, Mice, Phosphoproteins, Phosphorylation, Protein Interaction Maps, Protein Serine-Threonine Kinases, Proteomics, RNA Interference, Salmonella, Signal Transduction
Proc Natl Acad Sci U S A
Date: Dec. 11, 2020
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