Proton-sensing GPCR-YAP Signalling Promotes Cell Proliferation and Survival.

International Journal of Biological Sciences
Hongyi ZhuChangqing Zhang

Abstract

The pHs of extracellular fluids (ECFs) in humans are consistently maintained at 7.35 to 7.45 in physiological conditions. Pathological changes, including infarction, tumourigenesis and inflammation, commonly result in decreases in the ECF pH in the affected tissues. In this study, we report that proliferation is promoted and apoptosis is inhibited by decreases in extracellular pH. Furthermore, we demonstrated that proton-sensing G-protein-coupled receptors (GPCRs) are required for the pH-dependent regulation of proliferation and apoptosis through the G protein α subunit 12/13 (G12/13) and Rho GTPases. Next, we identified Yes-associated protein 1 (YAP) as a downstream effector of Rho signalling. Together, the results from our study demonstrate that extracellular pH can modulate cell proliferation and apoptosis by regulating the proton-sensing GPCR-YAP pathway.

Citations

May 11, 2019·Cells·Jiaqian Luo, Fa-Xing Yu
Nov 2, 2017·Oncotarget·Chunlin OuJian Ma
Aug 14, 2020·Scientific Reports·Nicola PiasentinRoberto Chignola
Jun 12, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Diana ZindelLaurent Prézeau
Jul 22, 2020·Developmental Cell·Consuelo Ibar, Kenneth D Irvine

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Methods Mentioned

BETA
amputation
flow cytometry
PCR
transgenic
GTPases
nuclear translocation
xenograft

Software Mentioned

Leica AF6000

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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