Figure 2.

The shedding hypothesis. Mutations in TNF receptor 1 (TNFR1) were thought to impair cleavage of TNFR1 from the membrane by membrane metalloproteases, leading to depletion in the pool of soluble TNF (sTNF) receptor (sTNFR1). In this model for TNF receptor-associated periodic syndrome mutations (TRAPS), both soluble and membrane-bound TNFα are no longer sequestered by the soluble receptor, resulting in overstimulation of membrane-bound TNFR1. NO, nitric oxide; ROS, reactive oxygen species.