{beta}-Barrel outer membrane proteins suppress mTORC2 activation and induce autophagic responses

The outer membranes of Gram-negative bacteria and mitochondria contain proteins with a distinct β-barrel tertiary structure that could function as a molecular pattern recognized by the innate immune system. Here, we report that purified outer membrane proteins (OMPs) from different bacterial and mitochondrial sources triggered the induction of autophagy-related endosomal acidification, LC3B lipidation, and p62 degradation. Furthermore, OMPs reduced the phosphorylation and therefore activation of the multiprotein complex mTORC2 and its substrate Akt in macrophages and epithelial cells. The cell surface receptor SlamF8 and the DNA-protein kinase subunit XRCC6 were required for these OMP-specific responses in macrophages and epithelial cells, respectively. The addition of OMPs to mouse bone marrow–derived macrophages infected with Salmonella Typhimurium facilitated bacterial clearance. These data identify a specific cellular response mediated by bacterial and mitochondrial OMPs that can alter inflammatory responses and influence the killing of pathogens.

Source: Signal Transduction Knowledge Environment - November 27, 2018 Category: Science Authors: Chaudhary, A., Kamischke, C., Leite, M., Altura, M. A., Kinman, L., Kulasekara, H., Blanc, M.-P., Wang, G., Terhorst, C., Miller, S. I. Tags: STKE Research Articles Source Type: news