title: The GOLD domain-containing protein TMED1 is involved in interleukin-33 signaling.
abstract: The proinflammatory danger signal IL-33, which is released from damaged or dying cells, achieves its effects via the IL-1R family member ST2L. The detection of IL-33 by ST2L initiates downstream signaling pathways that result in the activation of MAPKs and NF-κB. Here, we show that TMED1 associates with ST2L. Using a series of mutation and deletion constructs, we demonstrate that this interaction is mediated by the GOLD domain of TMED1 and the TIR domain of ST2L. Our findings also demonstrate that TMED1 is required for optimal IL-33-induced IL-8 and IL-6 production. This discovery provides additional support to the concept that the TMED family members are important players in innate immune signaling.
authors: Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland. connoldj@tcd.ie
authors: Dympna J
authors: DJ
authors: Connolly
authors: Luke A J
authors: LA
authors: O'Neill
authors: Anne F
authors: AF
authors: McGettrick
mesh_terms: D005786:Gene Expression Regulation; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007107:Immune System; D047468:Immunoprecipitation; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D018613:Microscopy, Confocal / Q000379:methods; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C580657:TMED1 protein, human; D033921:Vesicular Transport Proteins