Heteromerization of G2A and OGR1 enhances proton sensitivity and proton-induced calcium signals

Ya Han Huang, Yeu Shiuan Su, Chung Jen Chang, Wei Hsin Sun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Proton-sensing G-protein-coupled receptors (GPCRs; OGR1, GPR4, G2A, TDAG8), with full activation at pH 6.4 ∼ 6.8, are important to pH homeostasis, immune responses and acid-induced pain. Although G2A mediates the G13-Rho pathway in response to acid, whether G2A activates Gs, Gi or Gq proteins remains debated. In this study, we examined the response of this fluorescence protein-tagged OGR1 family to acid stimulation in HEK293T cells. G2A did not generate detectable intracellular calcium or cAMP signals or show apparent receptor redistribution with moderate acid (pH ≥ 6.0) stimulation but reduced cAMP accumulation under strong acid stimulation (pH ≤ 5.5). Surprisingly, coexpression of OGR1- and G2A-enhanced proton sensitivity and proton-induced calcium signals. This alteration is attributed to oligomerization of OGR1 and G2A. The oligomeric potential locates receptors at a specific site, which leads to enhanced proton-induced calcium signals through channels.

Original languageEnglish
Pages (from-to)633-644
Number of pages12
JournalJournal of Receptor and Signal Transduction Research
Issue number6
StatePublished - 1 Nov 2016


  • G-protein signaling
  • G2A
  • heteromerization
  • OGR1
  • Proton-sensing G protein-coupled receptor


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