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dc.contributor.authorNam, Alisha J.
dc.date.accessioned2020-06-16T17:23:57Z
dc.date.available2020-06-16T17:23:57Z
dc.date.issued2020-05
dc.identifier.urihttp://hdl.handle.net/10675.2/623390
dc.descriptionThis file is restricted to Augusta University. Please log in using your JagNet ID and password to access.en_US
dc.description.abstractG protein-coupled receptors (GPCRs) are membrane-bound receptors that can stimulate an intracellular signaling pathway following activation by a ligand. According to the International Union of Basic and Clinical Pharmacology (IUPHAR) database, GPR4, GPR65, and GPR132 are Class A orphan GPCRs with protons reported as their putative endogenous ligand. Because these receptors are currently understudied, the purpose of our study was to investigate the interactions between GPR4, GPR65 and GPR132 and G protein subtypes (Gαs, Gαi, Gαq, and Gα12) as a function of pH. Using bioluminescence resonance energy transfer (BRET), we studied the coupling between luciferase-tagged GPR receptors and fluorescent protein (Venus)-tagged heterotrimeric G proteins in response to changes in proton concentration. We found that all three receptors responded to pH changes. Upon extracellular response to pH changes, the receptors activate different G protein subtypes and thus, different signaling pathways: GPR4 activates all four G protein subtypes but has the strongest activation with Gαs; GPR65 activates all four subtypes; and GPR132 activates Gαi and weakly activates Gαq and Gα12. Identifying these receptors as true proton sensors leads the way in understanding the role they play in maintaining acid-base homeostasis and will be critical for the development of novel drugs combatting acidbase related disorders, such as ulcers and reflux esophagitis.en_US
dc.language.isoen_USen_US
dc.publisherAugusta Universityen_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.titleCharacterization of Potential Proton Sensitive G Protein-Coupled Receptorsen_US
dc.typeThesisen_US
dc.contributor.departmentDepartment of Biological Sciencesen_US
refterms.dateFOA2020-06-16T17:23:57Z


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