title: Heteromerization of G2A and OGR1 enhances proton sensitivity and proton-induced calcium signals.
abstract: 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.
authors.affiliation: a Department of Life Sciences , National Central University , Jhongli , Taiwan and.
authors.forename: Ya-Han
authors.initials: YH
authors.lastname: Huang
authors.affiliation: a Department of Life Sciences , National Central University , Jhongli , Taiwan and.
authors.forename: Yeu-Shiuan
authors.initials: YS
authors.lastname: Su
authors.affiliation: a Department of Life Sciences , National Central University , Jhongli , Taiwan and.
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: a Department of Life Sciences , National Central University , Jhongli , Taiwan and.|b Center for Biotechnology and Biomedical Engineering, National Central University , Jhongli , Taiwan.
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Sun
mesh_terms: D000143:Acids / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000737:chemistry; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055503:Protein Multimerization; D011522:Protons; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000143:Acids; D018797:Cell Cycle Proteins; C115270:G2A receptor; C486281:GPR68 protein, human; D011522:Protons; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP; D002118:Calcium
keywords: G-protein signaling; G2A; OGR1; Proton-sensing G protein-coupled receptor; heteromerization