Biased signaling by thyroid-stimulating hormone receptor-specific antibodies determines thyrocyte survival in autoimmunity.

ABSTRACT: The thyroid-stimulating hormone receptor (TSHR) is a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR). Autoimmune hyperthyroidism, commonly known as Graves' disease (GD), is caused by stimulating autoantibodies to the TSHR. We previously described TSHR-specific antibodies (TSHR-Abs) in GD that recognize linear epitopes in the cleavage region of the TSHR ectodomain (C-TSHR-Abs) and induce thyroid cell apoptosis instead of stimulating the TSHR. We found that C-TSHR-Abs entered the cell through clathrin-mediated endocytosis but did not trigger endosomal maturation and failed to undergo normal vesicular sorting and trafficking. We found that stimulating TSHR-Abs (S-TSHR-Abs) activated Gαs and, to a lesser extent, Gαq but that C-TSHR-Abs failed to activate a

SUBMITTER: Morshed SA 

PROVIDER: S-EPMC5812361 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature