Poster Presentation 2014 International Biophysics Congress

Heteromerization of G2A and OGR1 alters receptor location and proton-induced signaling pathway (#605)

Wei-Hsin Sun 1 , Ya-Han Huang 1 , Yeu-Shiuan Su 1 , Chung-Jen Chang 1
  1. National Central University, Jhongli, Taiwan

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. Whether G2A is a proton receptor remains debated because it did not generate a significant response after acid stimulation in previous studies. In this study, we examined the response of these fluorescence protein-tagged OGR1 family to acid stimulation in HEK293T cells. G2A was the only proton-sensing receptor that did not generate detectable intracellular calcium or show apparent receptor redistribution with acid stimulation. However, G2A reduced cAMP level after acid stimulation, suggesting it could mediate Gi protein activation. Interestingly, co-expression of OGR1 and G2A altered receptor location and the proton-induced signaling pathway. This alteration is attributed to oligomerization of OGR1 and G2A. The oligomeric potential locates receptors at a specific site, thus leading to enhanced proton-induced calcium signals through channels.