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.

Following exposure to pathogen-associated molecular patterns (PAMPs), the innate immune response and the subsequent inflammatory reaction rely on evolutionarily conserved receptors termed pattern-recognition receptors (PRRs) [1] . These signalling receptors can be expressed at the cellular membrane (Toll-like receptors (TLRs) 1, 2, 4, 5, and 6), in acidic endosomes (TLRs 3, 7, 8, and 9), or in the cytoplasmic compartment (the doublestranded RNA (dsRNA)-activated kinase (PKR); the RIG-I-like helicases (RLH): retinoic-acid-inducible gene I (RIG-I), melanoma differentiation antigen 5 (MDA5), and LGP2; the HIN-200 family members: Absent In Melanoma 2 (AIM2) and interferon (IFN)inducible IFI16 protein [2] ; the DNA-dependent activator of interferon regulatory factors (IRFs) (DAI) and the nucleotidebinding oligomerization domain (NOD) receptors). RIG-I and MDA5 have been characterized as important cytoplasmic sensors for viral RNA [3] [4] [5] [6] . Once activated by dsRNA molecules, RIG-I and MDA5 are recruited to the mitochondrial adaptor protein know as Mitochondrial AntiViral Signaling (MAVS) (also called IPS-1, Cardif and VISA) in order to trigger signalling cascades leading to IRF-3 and NF-kB activation, two essential players involved in the establishment of a cellular antiviral state [7] [8] [9] [10] .