Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/104800 https://doi.org/10.3390/ijms22158328 |
Resumo: | Protein-protein interactions between G protein-coupled receptors (GPCRs) can augment their functionality and increase the repertoire of signaling pathways they regulate. New therapeutics designed to modulate such interactions may allow for targeting of a specific GPCR activity, thus reducing potential for side effects. Dopamine receptor (DR) heteromers are promising candidates for targeted therapy of neurological conditions such as Parkinson's disease since current treatments can have severe side effects. To facilitate development of such therapies, it is necessary to identify the various DR binding partners. We report here a new interaction partner for DRD2 and DRD3, the orphan receptor G protein-coupled receptor 143 (GPR143), an atypical GPCR that plays multiple roles in pigment cells and is expressed in several regions of the brain. We previously demonstrated that the DRD2/ DRD3 antagonist pimozide also modulates GPR143 activity. Using confocal microscopy and two FRET methods, we observed that the DRs and GPR143 colocalize and interact at intracellular membranes. Furthermore, co-expression of wildtype GPR143 resulted in a 57% and 67% decrease in DRD2 and DRD3 activity, respectively, as determined by β-Arrestin recruitment assay. GPR143-DR dimerization may negatively modulate DR activity by changing affinity for dopamine or delaying delivery of the DRs to the plasma membrane. |
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Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143dopamine receptorsParkinson’s diseaseGPR143DRD2DRD3DopamineEye ProteinsHumansMembrane GlycoproteinsMutationProtein BindingReceptors, Dopamine D2Receptors, Dopamine D3Signal Transductionbeta-ArrestinsProtein Interaction Domains and MotifsProtein-protein interactions between G protein-coupled receptors (GPCRs) can augment their functionality and increase the repertoire of signaling pathways they regulate. New therapeutics designed to modulate such interactions may allow for targeting of a specific GPCR activity, thus reducing potential for side effects. Dopamine receptor (DR) heteromers are promising candidates for targeted therapy of neurological conditions such as Parkinson's disease since current treatments can have severe side effects. To facilitate development of such therapies, it is necessary to identify the various DR binding partners. We report here a new interaction partner for DRD2 and DRD3, the orphan receptor G protein-coupled receptor 143 (GPR143), an atypical GPCR that plays multiple roles in pigment cells and is expressed in several regions of the brain. We previously demonstrated that the DRD2/ DRD3 antagonist pimozide also modulates GPR143 activity. Using confocal microscopy and two FRET methods, we observed that the DRs and GPR143 colocalize and interact at intracellular membranes. Furthermore, co-expression of wildtype GPR143 resulted in a 57% and 67% decrease in DRD2 and DRD3 activity, respectively, as determined by β-Arrestin recruitment assay. GPR143-DR dimerization may negatively modulate DR activity by changing affinity for dopamine or delaying delivery of the DRs to the plasma membrane.MDPI AG2021-08-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/104800http://hdl.handle.net/10316/104800https://doi.org/10.3390/ijms22158328eng1422-0067Bueschbell, BeatrizManga, PrashielaPenner, ErikaSchiedel, Anke C.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-01-25T21:59:07Zoai:estudogeral.uc.pt:10316/104800Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:21:26.820633Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143 |
title |
Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143 |
spellingShingle |
Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143 Bueschbell, Beatriz dopamine receptors Parkinson’s disease GPR143 DRD2 DRD3 Dopamine Eye Proteins Humans Membrane Glycoproteins Mutation Protein Binding Receptors, Dopamine D2 Receptors, Dopamine D3 Signal Transduction beta-Arrestins Protein Interaction Domains and Motifs |
title_short |
Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143 |
title_full |
Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143 |
title_fullStr |
Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143 |
title_full_unstemmed |
Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143 |
title_sort |
Evidence for Protein-Protein Interaction between Dopamine Receptors and the G Protein-Coupled Receptor 143 |
author |
Bueschbell, Beatriz |
author_facet |
Bueschbell, Beatriz Manga, Prashiela Penner, Erika Schiedel, Anke C. |
author_role |
author |
author2 |
Manga, Prashiela Penner, Erika Schiedel, Anke C. |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Bueschbell, Beatriz Manga, Prashiela Penner, Erika Schiedel, Anke C. |
dc.subject.por.fl_str_mv |
dopamine receptors Parkinson’s disease GPR143 DRD2 DRD3 Dopamine Eye Proteins Humans Membrane Glycoproteins Mutation Protein Binding Receptors, Dopamine D2 Receptors, Dopamine D3 Signal Transduction beta-Arrestins Protein Interaction Domains and Motifs |
topic |
dopamine receptors Parkinson’s disease GPR143 DRD2 DRD3 Dopamine Eye Proteins Humans Membrane Glycoproteins Mutation Protein Binding Receptors, Dopamine D2 Receptors, Dopamine D3 Signal Transduction beta-Arrestins Protein Interaction Domains and Motifs |
description |
Protein-protein interactions between G protein-coupled receptors (GPCRs) can augment their functionality and increase the repertoire of signaling pathways they regulate. New therapeutics designed to modulate such interactions may allow for targeting of a specific GPCR activity, thus reducing potential for side effects. Dopamine receptor (DR) heteromers are promising candidates for targeted therapy of neurological conditions such as Parkinson's disease since current treatments can have severe side effects. To facilitate development of such therapies, it is necessary to identify the various DR binding partners. We report here a new interaction partner for DRD2 and DRD3, the orphan receptor G protein-coupled receptor 143 (GPR143), an atypical GPCR that plays multiple roles in pigment cells and is expressed in several regions of the brain. We previously demonstrated that the DRD2/ DRD3 antagonist pimozide also modulates GPR143 activity. Using confocal microscopy and two FRET methods, we observed that the DRs and GPR143 colocalize and interact at intracellular membranes. Furthermore, co-expression of wildtype GPR143 resulted in a 57% and 67% decrease in DRD2 and DRD3 activity, respectively, as determined by β-Arrestin recruitment assay. GPR143-DR dimerization may negatively modulate DR activity by changing affinity for dopamine or delaying delivery of the DRs to the plasma membrane. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-03 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/104800 http://hdl.handle.net/10316/104800 https://doi.org/10.3390/ijms22158328 |
url |
http://hdl.handle.net/10316/104800 https://doi.org/10.3390/ijms22158328 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1422-0067 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI AG |
publisher.none.fl_str_mv |
MDPI AG |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134105112150016 |