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GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells

Receptor-receptor interactions are essential to fine tune receptor responses and new techniques enable closer characterization of the interactions between involved proteins directly in the plasma membrane. Fluorescence cross-correlation spectroscopy (FCCS), which analyses concurrent movement of boun...

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Autores principales: Hertz, E., Terenius, L., Vukojević, V., Svenningsson, P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pergamon Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599889/
https://www.ncbi.nlm.nih.gov/pubmed/30423289
http://dx.doi.org/10.1016/j.neuropharm.2018.11.009
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author Hertz, E.
Terenius, L.
Vukojević, V.
Svenningsson, P.
author_facet Hertz, E.
Terenius, L.
Vukojević, V.
Svenningsson, P.
author_sort Hertz, E.
collection PubMed
description Receptor-receptor interactions are essential to fine tune receptor responses and new techniques enable closer characterization of the interactions between involved proteins directly in the plasma membrane. Fluorescence cross-correlation spectroscopy (FCCS), which analyses concurrent movement of bound molecules with single-molecule detection limit, was here used to, in live N2a cells, study interactions between the Parkinson's disease (PD) associated orphan receptor GPR37, its homologue GPR37L1, and the two splice variants of the dopamine 2 receptor (D2R). An interaction between GPR37 and both splice forms of D2R was detected. 4-phenylbutyrate (4-PBA), a neuroprotective chemical chaperone known to increase GPR37 expression at the cell surface, increased the fraction of interacting molecules. The interaction was also increased by pramipexole, a D2R agonist commonly used in the treatment of PD, indicating a possible clinically relevance. Cross-correlation, indicating interaction between GPR37L1 and the short isoform of D2R, was also detected. However, this interaction was not changed with 4-PBA or pramipexole treatment. Overall, these data provide further evidence that heteromeric GPR37-D2R exist and can be pharmacologically modulated, which is relevant for the treatment of PD. This article is part of the Special Issue entitled ‘Receptor heteromers and their allosteric receptor-receptor interactions’.
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spelling pubmed-65998892019-07-12 GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells Hertz, E. Terenius, L. Vukojević, V. Svenningsson, P. Neuropharmacology Article Receptor-receptor interactions are essential to fine tune receptor responses and new techniques enable closer characterization of the interactions between involved proteins directly in the plasma membrane. Fluorescence cross-correlation spectroscopy (FCCS), which analyses concurrent movement of bound molecules with single-molecule detection limit, was here used to, in live N2a cells, study interactions between the Parkinson's disease (PD) associated orphan receptor GPR37, its homologue GPR37L1, and the two splice variants of the dopamine 2 receptor (D2R). An interaction between GPR37 and both splice forms of D2R was detected. 4-phenylbutyrate (4-PBA), a neuroprotective chemical chaperone known to increase GPR37 expression at the cell surface, increased the fraction of interacting molecules. The interaction was also increased by pramipexole, a D2R agonist commonly used in the treatment of PD, indicating a possible clinically relevance. Cross-correlation, indicating interaction between GPR37L1 and the short isoform of D2R, was also detected. However, this interaction was not changed with 4-PBA or pramipexole treatment. Overall, these data provide further evidence that heteromeric GPR37-D2R exist and can be pharmacologically modulated, which is relevant for the treatment of PD. This article is part of the Special Issue entitled ‘Receptor heteromers and their allosteric receptor-receptor interactions’. Pergamon Press 2019-07-01 /pmc/articles/PMC6599889/ /pubmed/30423289 http://dx.doi.org/10.1016/j.neuropharm.2018.11.009 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hertz, E.
Terenius, L.
Vukojević, V.
Svenningsson, P.
GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells
title GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells
title_full GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells
title_fullStr GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells
title_full_unstemmed GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells
title_short GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells
title_sort gpr37 and gpr37l1 differently interact with dopamine 2 receptors in live cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599889/
https://www.ncbi.nlm.nih.gov/pubmed/30423289
http://dx.doi.org/10.1016/j.neuropharm.2018.11.009
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