Proton-sensing GPCR-YAP Signalling Promotes Cell Proliferation and Survival.
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.
1. Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Hongyi
H
Zhu
1. Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China. ; 2. Institute of Microsurgery on Extremities, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Xiangguo
X
Cheng
2. Institute of Microsurgery on Extremities, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Xin
X
Niu
1. Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Yuelei
Y
Zhang
1. Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Junjie
J
Guan
1. Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Xiaolin
X
Liu
1. Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Shicong
S
Tao
1. Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China. ; 2. Institute of Microsurgery on Extremities, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Yang
Y
Wang
1. Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China. ; 2. Institute of Microsurgery on Extremities, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Changqing
C
Zhang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D054460:rho-Associated Kinases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D054460:rho-Associated Kinases
GPCR; YAP; apoptosis; pH; proliferation; proton-sensing