Modulation of GPR133 (ADGRD1) Signaling by its Intracellular Interaction Partner Extended Synaptotagmin 1 (ESYT1).

ABSTRACT: GPR133 (ADGRD1) is an adhesion G protein-coupled receptor that signals through Gαs and is required for growth of glioblastoma (GBM), an aggressive brain malignancy. The regulation of GPR133 signaling is incompletely understood. Here, we use proximity biotinylation proteomics to identify ESYT1, a Ca²⁺-dependent mediator of endoplasmic reticulum-plasma membrane bridge formation, as an intracellular interactor of GPR133. ESYT1 knockdown or knockout increases GPR133 signaling, while its overexpression has the opposite effect, without altering GPR133 levels in the plasma membrane. The GPR133-ESYT1 interaction requires the Ca²⁺-sensing C2C domain of ESYT1. Thapsigargin-mediated increases in cytosolic Ca²⁺ relieve signaling-suppressive effects of ESYT1 by promotin

SUBMITTER: Stephan G 

PROVIDER: S-EPMC9934660 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature