A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate β-arrestin-biased signaling.

ABSTRACT: The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that signals through G_q/11 and G_i/o to stimulate cytosolic calcium (Ca²⁺_i) and mitogen-activated protein kinase (MAPK) signaling to control extracellular calcium homeostasis. Studies of loss- and gain-of-function CASR mutations, which cause familial hypocalciuric hypercalcemia type 1 (FHH1) and autosomal dominant hypocalcemia type 1 (ADH1), respectively, have revealed that the CaSR signals in a biased manner. Thus, some mutations associated with FHH1 lead to signaling predominantly through the MAPK pathway, whereas mutations associated with ADH1 preferentially enhance Ca²⁺_i responses. We report a previously unidentified ADH1-associated R680G Ca

SUBMITTER: Gorvin CM 

PROVIDER: S-EPMC6166785 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature