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.

Here, we have used a proteomics-based strategy to identify novel TRAF3 interacting proteins that are implicated in the induction of type I IFN. Using this approach, we have identified two novel TRAF3 interactors, Sec16A (also known as KIAA0310) and p115 (also known as USO1), which have characterized roles in the Endoplasmic Reticulum (ER)-to-Golgi vesicular transport system. Both proteins were shown to play a primary role in the anterograde trafficking at the ER-Golgi interface by influencing the assembly and transport of coat protein complex II (COPII) vesicles. Sec16A assembles on the ER membrane and forms organized scaffold defining ER exit sites (ERES) where COPII assembly occurs [23] [24] [25] . The coiled-coil myosin-shaped molecule p115 was demonstrated to be an important tethering adaptor, which mediates vesicle tethering at the ER [26] , Endoplasmatic Reticulum-Golgi Intermediate Compartment (ERGIC) [27] , and in conjunction with tether proteins giantin and GM130 at the cis-Golgi [28, 29] .