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Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain
G protein-coupled receptors (GPCRs) constitute the largest group of membrane receptor proteins controlling brain activity. Accordingly, GPCRs are the main target of commercial drugs for most neurological and neuropsychiatric disorders. One of the mechanisms by which GPCRs regulate neuronal function...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bentham Science Publishers
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886828/ https://www.ncbi.nlm.nih.gov/pubmed/34736381 http://dx.doi.org/10.2174/1570159X19666211104145727 |
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author | Fernández-Dueñas, Víctor Bonaventura, Jordi Aso, Ester Luján, Rafael Ferré, Sergi Ciruela, Francisco |
author_facet | Fernández-Dueñas, Víctor Bonaventura, Jordi Aso, Ester Luján, Rafael Ferré, Sergi Ciruela, Francisco |
author_sort | Fernández-Dueñas, Víctor |
collection | PubMed |
description | G protein-coupled receptors (GPCRs) constitute the largest group of membrane receptor proteins controlling brain activity. Accordingly, GPCRs are the main target of commercial drugs for most neurological and neuropsychiatric disorders. One of the mechanisms by which GPCRs regulate neuronal function is by homo- and heteromerization, with the establishment of direct protein-protein interactions between the same and different GPCRs. The occurrence of GPCR homo- and heteromers in artificial systems is generally well accepted, but more specific methods are necessary to address GPCR oligomerization in the brain. Here, we revise some of the techniques that have mostly contributed to reveal GPCR oligomers in native tissue, which include immunogold electron microscopy, proximity ligation assay (PLA), resonance energy transfer (RET) between fluorescent ligands and the Amplified Luminescent Proximity Homogeneous Assay (ALPHA). Of note, we use the archetypical GPCR oligomer, the adenosine A(2A) receptor (A(2A)R)-dopamine D(2) receptor (D(2)R) heteromer as an example to illustrate the implementation of these techniques, which can allow visualizing GPCR oligomers in the human brain under normal and pathological conditions. Indeed, GPCR oligomerization may be involved in the pathophysiology of neurological and neuropsychiatric disorders. |
format | Online Article Text |
id | pubmed-9886828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-98868282023-02-09 Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain Fernández-Dueñas, Víctor Bonaventura, Jordi Aso, Ester Luján, Rafael Ferré, Sergi Ciruela, Francisco Curr Neuropharmacol Neurology G protein-coupled receptors (GPCRs) constitute the largest group of membrane receptor proteins controlling brain activity. Accordingly, GPCRs are the main target of commercial drugs for most neurological and neuropsychiatric disorders. One of the mechanisms by which GPCRs regulate neuronal function is by homo- and heteromerization, with the establishment of direct protein-protein interactions between the same and different GPCRs. The occurrence of GPCR homo- and heteromers in artificial systems is generally well accepted, but more specific methods are necessary to address GPCR oligomerization in the brain. Here, we revise some of the techniques that have mostly contributed to reveal GPCR oligomers in native tissue, which include immunogold electron microscopy, proximity ligation assay (PLA), resonance energy transfer (RET) between fluorescent ligands and the Amplified Luminescent Proximity Homogeneous Assay (ALPHA). Of note, we use the archetypical GPCR oligomer, the adenosine A(2A) receptor (A(2A)R)-dopamine D(2) receptor (D(2)R) heteromer as an example to illustrate the implementation of these techniques, which can allow visualizing GPCR oligomers in the human brain under normal and pathological conditions. Indeed, GPCR oligomerization may be involved in the pathophysiology of neurological and neuropsychiatric disorders. Bentham Science Publishers 2022-05-16 2022-05-16 /pmc/articles/PMC9886828/ /pubmed/34736381 http://dx.doi.org/10.2174/1570159X19666211104145727 Text en © 2022 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Neurology Fernández-Dueñas, Víctor Bonaventura, Jordi Aso, Ester Luján, Rafael Ferré, Sergi Ciruela, Francisco Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain |
title | Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain |
title_full | Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain |
title_fullStr | Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain |
title_full_unstemmed | Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain |
title_short | Overcoming the Challenges of Detecting GPCR Oligomerization in the Brain |
title_sort | overcoming the challenges of detecting gpcr oligomerization in the brain |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886828/ https://www.ncbi.nlm.nih.gov/pubmed/34736381 http://dx.doi.org/10.2174/1570159X19666211104145727 |
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