GPCR heteromers: An overview of their classification, function and physiological relevance
G protein-coupled receptors (GPCRs) are capable of interacting to form higher order structures such as homomers and heteromers. Heteromerisation in particular has implications for receptor function, with research showing receptors can attain unique expression, ligand binding, signalling and intracel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.931573/full |
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| author | Natasha C. Dale Natasha C. Dale Elizabeth K. M. Johnstone Elizabeth K. M. Johnstone Elizabeth K. M. Johnstone Kevin D. G. Pfleger Kevin D. G. Pfleger Kevin D. G. Pfleger |
| author_facet | Natasha C. Dale Natasha C. Dale Elizabeth K. M. Johnstone Elizabeth K. M. Johnstone Elizabeth K. M. Johnstone Kevin D. G. Pfleger Kevin D. G. Pfleger Kevin D. G. Pfleger |
| author_sort | Natasha C. Dale |
| collection | DOAJ |
| description | G protein-coupled receptors (GPCRs) are capable of interacting to form higher order structures such as homomers and heteromers. Heteromerisation in particular has implications for receptor function, with research showing receptors can attain unique expression, ligand binding, signalling and intracellular trafficking upon heteromerisation. As such, GPCR heteromers represent novel drug targets with extensive therapeutic potential. Changes to ligand affinity, efficacy and G protein coupling have all been described, with alterations to these pharmacological aspects now well accepted as common traits for heteromeric complexes. Changes in internalisation and trafficking kinetics, as well as β-arrestin interactions are also becoming more apparent, however, few studies to date have explicitly looked at the implications these factors have upon the signalling profile of a heteromer. Development of ligands to target GPCR heteromers both experimentally and therapeutically has been mostly concentrated on bivalent ligands due to difficulties in identifying and developing heteromer-specific ligands. Improving our understanding of the pharmacology and physiology of GPCR heteromers will enable further development of heteromer-specific ligands with potential to provide therapeutics with increased efficacy and decreased side effects. |
| first_indexed | 2024-12-10T18:07:26Z |
| format | Article |
| id | doaj.art-bca4f33656444636bc98420ffa0346bc |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-10T18:07:26Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-bca4f33656444636bc98420ffa0346bc2022-12-22T01:38:35ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-08-011310.3389/fendo.2022.931573931573GPCR heteromers: An overview of their classification, function and physiological relevanceNatasha C. Dale0Natasha C. Dale1Elizabeth K. M. Johnstone2Elizabeth K. M. Johnstone3Elizabeth K. M. Johnstone4Kevin D. G. Pfleger5Kevin D. G. Pfleger6Kevin D. G. Pfleger7Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA, AustraliaAustralian Research Council Centre for Personalised Therapeutics Technologies, Perth, WA, AustraliaMolecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA, AustraliaAustralian Research Council Centre for Personalised Therapeutics Technologies, Perth, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Nedlands, WA, AustraliaMolecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Nedlands, WA, AustraliaAustralian Research Council Centre for Personalised Therapeutics Technologies, Perth, WA, AustraliaDimerix Limited, Nedlands, AustraliaG protein-coupled receptors (GPCRs) are capable of interacting to form higher order structures such as homomers and heteromers. Heteromerisation in particular has implications for receptor function, with research showing receptors can attain unique expression, ligand binding, signalling and intracellular trafficking upon heteromerisation. As such, GPCR heteromers represent novel drug targets with extensive therapeutic potential. Changes to ligand affinity, efficacy and G protein coupling have all been described, with alterations to these pharmacological aspects now well accepted as common traits for heteromeric complexes. Changes in internalisation and trafficking kinetics, as well as β-arrestin interactions are also becoming more apparent, however, few studies to date have explicitly looked at the implications these factors have upon the signalling profile of a heteromer. Development of ligands to target GPCR heteromers both experimentally and therapeutically has been mostly concentrated on bivalent ligands due to difficulties in identifying and developing heteromer-specific ligands. Improving our understanding of the pharmacology and physiology of GPCR heteromers will enable further development of heteromer-specific ligands with potential to provide therapeutics with increased efficacy and decreased side effects.https://www.frontiersin.org/articles/10.3389/fendo.2022.931573/fullG protein-coupled receptors (GPCRs)heteromerdimerbiased signallingβ-arrestinendocytosis |
| spellingShingle | Natasha C. Dale Natasha C. Dale Elizabeth K. M. Johnstone Elizabeth K. M. Johnstone Elizabeth K. M. Johnstone Kevin D. G. Pfleger Kevin D. G. Pfleger Kevin D. G. Pfleger GPCR heteromers: An overview of their classification, function and physiological relevance Frontiers in Endocrinology G protein-coupled receptors (GPCRs) heteromer dimer biased signalling β-arrestin endocytosis |
| title | GPCR heteromers: An overview of their classification, function and physiological relevance |
| title_full | GPCR heteromers: An overview of their classification, function and physiological relevance |
| title_fullStr | GPCR heteromers: An overview of their classification, function and physiological relevance |
| title_full_unstemmed | GPCR heteromers: An overview of their classification, function and physiological relevance |
| title_short | GPCR heteromers: An overview of their classification, function and physiological relevance |
| title_sort | gpcr heteromers an overview of their classification function and physiological relevance |
| topic | G protein-coupled receptors (GPCRs) heteromer dimer biased signalling β-arrestin endocytosis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.931573/full |
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