Immunoediting role for major vault protein in apoptotic signaling induced by bacterial <i>N</i> -acyl homoserine lactones
Josep Rayó, Rachel Gregor, Nicholas T. Jacob, Rambabu Dandela, Luba Dubinsky, Alex Yashkin, Alexander Aranovich, M. Thangaraj, Orna Ernst, Eran Barash, Sergey Malitsky, Bogdan I. Florea, Bastiaan P. Krom, Erik A.C. Wiemer, Valerie A. Kickhoefer, Leonard H. Rome, John C. Mathison, Gunnar F. Kaufmann, Herman S. Overkleeft, Benjamin F. Cravatt, Tsaffrir Zor, Kim D. Janda, Richard J. Ulevitch, Vladimir V. Kravchenko, Michaël M. Meijler
Abstract
-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL).