Figure 4

Signalling and trafficking pathways for wild-type and mutant TNF receptor 1. In TNF receptor-associated periodic syndrome mutations (TRAPS) patient cells, mutant TNF receptor 1 (TNFR1) are retained in the endoplasmic reticulum (ER) as disulphide-linked oligomers while the wild-type (WT) receptors traffic to the cell surface, leaving TNFα-induced NF-κB activation intact. ER-retained oligomers may independently activate novel signalling pathways leading to inflammation, may modify ER stress-induced responses, or may block TNFα-induced apoptosis. Mutant TNFR1 does not contribute to the antagonistic pool of soluble TNFR1 because it does not bind ligand. CRP, C-reactive protein; SAA, serum amyloid A; sTNFR1, soluble TNFR1.