Proteomic Profiling of the TRAF3 Interactome Network Reveals a New Role for the ER-to-Golgi Transport Compartments in Innate Immunity

van Zuylen, Wendy J.; Doyon, Priscilla; Clément, Jean-François; Khan, Kashif Aziz; D'Ambrosio, Lisa M.; Dô, Florence; St-Amant-Verret, Myriam; Wissanji, Tasheen; Emery, Gregory; Gingras, Anne-Claude; Meloche, Sylvain; Servant, Marc J.

Our data demonstrate that TRAF3 does not associate with the mitochondrial network in resting cells ( Figure 2A, panel 8) . However, TRAF3 was demonstrated to link the mitochondrial membrane-bound protein MAVS to the activation of TBK1, which is required for IRF3/7 phosphorylation and type I IFN induction in response to viral infection [20, 47] . Therefore, we next addressed the subcellular localization of endogenous TRAF3 upon viral infection and RNA/DNA sensor pathway activation. Intracellular delivery of the double-stranded RNA mimicry molecule, poly I:C, or the dsDNA mimicry agent poly dA:dT resulted in disorganization of the ribbon-like structure of the Golgi apparatus, giving rise to the formation of Golgi ministacks containing GM130 ( Figure 4A , arrows in panel 2 and 3). Importantly, the localization of endogenous TRAF3 followed these Golgi fragments. Similar observations were made in cells infected with RIG-I inducers, Sendai virus (SeV), Respiratory Syncytial Virus (RSV) and Influenza virus ( Figure 4B ).