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PERP,a host tetraspanning membrane protein,is required for Salmonella‐induced inflammation
Authors:Kelly N Hallstrom  C V Srikanth  Terence A Agbor  Christopher M Dumont  Kristen N Peters  Luminita Paraoan  James E Casanova  Erik J Boll  Beth A McCormick
Affiliation:1. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA;2. Eye and Vision Science Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK;3. Department of Cell Biology, University of Virginia Health System, Charlottesville, VA, USA
Abstract:Salmonella enterica Typhimurium induces intestinal inflammation through the activity of type III secreted effector (T3SE) proteins. Our prior results indicate that the secretion of the T3SE SipA and the ability of SipA to induce epithelial cell responses that lead to induction of polymorphonuclear transepithelial migration are not coupled to its direct delivery into epithelial cells from Salmonella. We therefore tested the hypothesis that SipA interacts with a membrane protein located at the apical surface of intestinal epithelial cells. Employing a split ubiquitin yeast‐two‐hybrid screen, we identified the tetraspanning membrane protein, p53 effector related to PMP‐22 (PERP), as a SipA binding partner. SipA and PERP appear to have intersecting activities as we found PERP to be involved in proinflammatory pathways shown to be regulated by SipA. In sum, our studies reveal a critical role for PERP in the pathogenesis of S. Typhimurium, and for the first time demonstrate that SipA, a T3SE protein, can engage a host protein at the epithelial surface.
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