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Construction of Model Lipid Membranes Incorporating G-protein Coupled Receptors (GPCRs)
Published on: February 5, 2022
Receptors for protons or lipid messengers or both?
Klaus Seuwen1, Marie-Gabrielle Ludwig, Romain M Wolf
1Novartis Institutes for Biomedical Research, Basel, Switzerland. klaus.seuwen@novartis.com
Journal of Receptor and Signal Transduction Research
|November 23, 2006
Summary
GPR4, OGR1, and TDAG8 are confirmed proton-sensing receptors, challenging their prior classification as lipid receptors. This research clarifies their role in sensing acidic pH, crucial for physiological understanding.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- G protein-coupled receptors (GPCRs) like GPR4, OGR1, TDAG8, and G2A were initially identified as receptors for lipid messengers such as sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC).
- Retractions of key publications and emerging research have questioned this initial characterization, suggesting alternative functions for this receptor family.
Purpose of the Study:
- To re-evaluate the primary function of the GPR4 subfamily of GPCRs.
- To confirm whether these receptors sense acidic pH or lipid messengers.
- To provide a current perspective on the classification and function of GPR4, OGR1, and TDAG8.
Main Methods:
- Experimental validation of proton-sensing capabilities for GPR4, OGR1, and TDAG8.
- Assessment of the influence of sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC) on receptor activity at varying pH levels.
- Review of existing literature and retracted studies concerning these receptors.
Main Results:
- GPR4, OGR1, and TDAG8 function as proton-sensing receptors, responding to changes in acidic pH.
- The previously reported agonistic effects of SPC and LPC on these receptors were not consistently observed under acidic conditions.
- High concentrations of lipids showed non-specific negative regulation of these proton-sensing receptors.
Conclusions:
- GPR4, OGR1, and TDAG8 should be definitively classified as proton-sensing receptors.
- The role of these receptors in physiological processes is primarily linked to pH sensing, not lipid signaling.
- Previous findings implicating lipids as specific agonists for this receptor family are now considered inaccurate.
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