mProX™ Human GPR52 Stable Cell Line

Power ME, et al. "The non-nutritive sweetener sucralose increases beta-arrestin signaling at the ." Canadian journal of physiology and pharmacology, 2023.
In recent years, there has been a rise in the use of non-nutritive sweeteners in food products due to their low caloric content and strong sweetness compared to natural sugars. Despite evidence supporting their safety, there are studies contradicting this, suggesting that sweeteners may have negative effects on metabolism through unknown mechanisms. The authors propose that these sweeteners activate specific G protein-coupled receptors (GPCRs), particularly orphan receptors found in metabolically active tissues. Through a beta-arrestin-2 recruitment assay, the response of 64 orphan receptors to the sweeteners sucralose and saccharin was measured. It was found that GPR52 was the only receptor that significantly responded to the mixture of both sweeteners, with subsequent experiments revealing sucralose as the activating sweetener. This activation was concentration-dependent and did not further activate the receptor's CRE pathway, which is known to be constitutively active. This novel interaction between sucralose and GPR52 raises questions about the assumed lack of biological activity of sucralose, indicating the potential for off-target signaling through the activation of GPR52.
Pubmed: 37748201   DOI: 10.1139/cjpp-2023-0199

Wu Z, et al. "Dynamic Insights into the Self-Activation Pathway and Allosteric Regulation of ." Journal of chemical information and modeling, 2023.
The subject of this abstract explored the mechanism of action for orphan G-protein-coupled receptor 52 (GPR52), which has been identified as a promising therapeutic target for central nervous system disorders. Through 6 mus Gaussian accelerated molecular dynamics (GaMD) simulations, the receptor demonstrated a self-activation pathway in which it transitions from an active state to a matching inactive crystal structure. The results also revealed the allosteric regulation between the extracellular orthosteric binding pocket and the intracellular G-protein-binding site, identifying key microswitch residues and the allosteric communication pathway. The role of ECL2 in this allosteric regulation was further supported by transfer entropy calculations. Overall, this work provides a detailed atomic-level understanding of the self-activation of GPR52, shedding light on a potential target for novel drug development.
Pubmed: 37651308   DOI: 10.1021/acs.jcim.3c00672