Figure 2: A proposed model for the inhibitory effect of anti-muscarinic autoantibodies. pSS IgG inhibits M3R function in two ways. At the early stage, M3R is acutely desensitized by direct occupation of agonist binding sites of the receptor by pSS IgG, which induce phosphorylation of the receptor (A). In the continued presence of pSS IgG, M3R function is further decreased by its internalization (B) and degradation (C) through the clathrin-mediated pathway. After internalization of M3R, abundant pSS IgG may bind to unoccupied M3Rs, resulting in a progressive and long-term loss of M3R function.