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.

Since novel essential mediators of the type I IFN response were recently found to be associated with the ER or the exocyst pathway, such as STING (also called MITA, ERIS, and MPYS), Sec61b and Sec5 [30] [31] [32] [33] , we postulated that Sec16A and p115 may exert a similar function through the ER-to-Golgi transport compartments. Co-immunoprecipitation experiments and confocal microscopy confirmed the association and co-localization of TRAF3 with p115 and Sec16A. Importantly, overexpression of p115 or Sec16A increased the type I IFN response, whereas their knockdown impaired the induction of antiviral genes. Interestingly, the Golgi apparatus fragmented into cytoplasmic punctate structures following both RLH and cytoplasmic DNA sensor pathway activation, allowing TRAF3 to colocalize and associate with MAVS. Our study identifies p115 and Sec16A as new scaffold proteins involved in the establishment of the antiviral state.