Identification of Gain and Loss of Function Missense Variants in MRGPRX2's Transmembrane and Intracellular Domains for Mast Cell Activation by Substance P.

ABSTRACT: The neuropeptide substance P (SP) contributes to neurogenic inflammation through the activation of human mast cells via Mas-related G protein-coupled receptor-X2 (MRGPRX2). Using pertussis toxins and YM-254890, we demonstrated that SP induces Ca²⁺ mobilization and degranulation via both the Gαi and Gαq family of G proteins in rat basophilic leukemia (RBL-2H3) cells stably expressing MRGPRX2. To determine the roles of MRGPRX2's transmembrane (TM) and intracellular domains on SP-induced responses, we utilized information obtained from both structural modeling and naturally occurring MRGPRX2 missense variants. We found that highly conserved residues in TM6 (I225) and TM7 (Y279) of MRGPRX2 are essential for SP-induced Ca²⁺ mobilization and degranulation in transiently tra

SUBMITTER: Chompunud Na Ayudhya C 

PROVIDER: S-EPMC6862462 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature