Extracellular calcium alters calcium-sensing receptor network integrating intracellular calcium-signaling and related key pathway

14Citations
Citations of this article
28Readers
Mendeley users who have this article in their library.

Abstract

G-protein-coupled receptors (GPCRs) are a target for over 34% of current drugs. The calcium-sensing receptor (CaSR), a family C GPCR, regulates systemic calcium (Ca2+) homeostasis that is critical for many physiological, calciotropical, and noncalciotropical outcomes in multiple organs. However, the mechanisms by which extracellular Ca2+ (Ca2+ex) and the CaSR mediate networks of intracellular Ca2+-signaling and players involved throughout the life cycle of CaSR are largely unknown. Here we report the first CaSR protein–protein interactome with 94 novel putative and 8 previously published interactors using proteomics. Ca2+ex promotes enrichment of 66% of the identified CaSR interactors, pertaining to Ca2+ dynamics, endocytosis, degradation, trafficking, and primarily to protein processing in the endoplasmic reticulum (ER). These enhanced ER-related processes are governed by Ca2+ex-activated CaSR which directly modulates ER-Ca2+ (Ca2+ER), as monitored by a novel ER targeted Ca2+-sensor. Moreover, we validated the Ca2+ex dependent colocalizations and interactions of CaSR with ER-protein processing chaperone, 78-kDa glucose regulated protein (GRP78), and with trafficking-related protein. Live cell imaging results indicated that CaSR and vesicle-associated membrane protein-associated A (VAPA) are inter-dependent during Ca2+ex induced enhancement of near-cell membrane expression. This study significantly extends the repertoire of the CaSR interactome and reveals likely novel players and pathways of CaSR participating in Ca2+ER dynamics, agonist mediated ER-protein processing and surface expression.

Cite

CITATION STYLE

APA

Gorkhali, R., Tian, L., Dong, B., Bagchi, P., Deng, X., Pawar, S., … Yang, J. (2021). Extracellular calcium alters calcium-sensing receptor network integrating intracellular calcium-signaling and related key pathway. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-00067-2

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free