GPR31 and GPR151 are activated under acidic conditions

Area of Science:

• Physiology
• Molecular Biology
• Biochemistry

Background:

• Extracellular proton sensing is crucial for cellular function.
• Several G protein-coupled receptors (GPCRs) like OGR1, GPR4, G2A, and TDAG8 are known proton sensors.
• The full repertoire of proton-sensing GPCRs remains incompletely characterized.

Purpose of the Study:

• To investigate the potential of GPR31 and GPR151 as novel proton-sensing GPCRs.
• To characterize the pH sensitivity and activation mechanisms of GPR31 and GPR151.

Main Methods:

• Utilized [35S]GTPγS binding assays with GPR31-Giα and GPR151-Giα fusion proteins.
• Performed reporter gene assays in CHO cells expressing recombinant GPR31 or GPR151.
• Assessed receptor activation across a range of extracellular pH conditions.

Main Results:

• GPR31 and GPR151 exhibited activation in acidic conditions.
• Receptor activation showed a notable increase between pH 6 and 5, with maximal activation around pH 5.8.
• [35S]GTPγS binding assays and reporter gene assays confirmed proton-sensing capabilities.

Conclusions:

• GPR31 and GPR151 function as proton-sensing GPCRs.
• These receptors demonstrate comparable proton-sensing abilities to previously identified GPCRs.
• The findings expand the known family of extracellular pH-sensing receptors.