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GM1 Is Cytoprotective in GPR37-Expressing Cells and Downregulates Signaling
G-protein-coupled receptors (GPCRs) are commonly pharmacologically modulated due to their ability to translate extracellular events to intracellular changes. Previously, studies have mostly focused on protein–protein interactions, but the focus has now expanded also to protein–lipid connections. GM1...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657933/ https://www.ncbi.nlm.nih.gov/pubmed/34884663 http://dx.doi.org/10.3390/ijms222312859 |
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author | Hertz, Ellen Saarinen, Marcus Svenningsson, Per |
author_facet | Hertz, Ellen Saarinen, Marcus Svenningsson, Per |
author_sort | Hertz, Ellen |
collection | PubMed |
description | G-protein-coupled receptors (GPCRs) are commonly pharmacologically modulated due to their ability to translate extracellular events to intracellular changes. Previously, studies have mostly focused on protein–protein interactions, but the focus has now expanded also to protein–lipid connections. GM1, a brain-expressed ganglioside known for neuroprotective effects, and GPR37, an orphan GPCR often reported as a potential drug target for diseases in the central nervous system, have been shown to form a complex. In this study, we looked into the functional effects. Endogenous GM1 was downregulated when stably overexpressing GPR37 in N2a cells (N2a(GPR37-eGFP)). However, exogenous GM1 specifically rescued N2a(GPR37-eGFP) from toxicity induced by the neurotoxin MPP+. The treatment did not alter transcription levels of GPR37 or the enzyme responsible for GM1 production, both potential mechanisms for the effect. However, GM1 treatment inhibited cAMP-dependent signaling from GPR37, here reported as potentially consecutively active, possibly contributing to the protective effects. We propose an interplay between GPR37 and GM1 as one of the many cytoprotective effects reported for GM1. |
format | Online Article Text |
id | pubmed-8657933 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86579332021-12-10 GM1 Is Cytoprotective in GPR37-Expressing Cells and Downregulates Signaling Hertz, Ellen Saarinen, Marcus Svenningsson, Per Int J Mol Sci Communication G-protein-coupled receptors (GPCRs) are commonly pharmacologically modulated due to their ability to translate extracellular events to intracellular changes. Previously, studies have mostly focused on protein–protein interactions, but the focus has now expanded also to protein–lipid connections. GM1, a brain-expressed ganglioside known for neuroprotective effects, and GPR37, an orphan GPCR often reported as a potential drug target for diseases in the central nervous system, have been shown to form a complex. In this study, we looked into the functional effects. Endogenous GM1 was downregulated when stably overexpressing GPR37 in N2a cells (N2a(GPR37-eGFP)). However, exogenous GM1 specifically rescued N2a(GPR37-eGFP) from toxicity induced by the neurotoxin MPP+. The treatment did not alter transcription levels of GPR37 or the enzyme responsible for GM1 production, both potential mechanisms for the effect. However, GM1 treatment inhibited cAMP-dependent signaling from GPR37, here reported as potentially consecutively active, possibly contributing to the protective effects. We propose an interplay between GPR37 and GM1 as one of the many cytoprotective effects reported for GM1. MDPI 2021-11-27 /pmc/articles/PMC8657933/ /pubmed/34884663 http://dx.doi.org/10.3390/ijms222312859 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Hertz, Ellen Saarinen, Marcus Svenningsson, Per GM1 Is Cytoprotective in GPR37-Expressing Cells and Downregulates Signaling |
title | GM1 Is Cytoprotective in GPR37-Expressing Cells and Downregulates Signaling |
title_full | GM1 Is Cytoprotective in GPR37-Expressing Cells and Downregulates Signaling |
title_fullStr | GM1 Is Cytoprotective in GPR37-Expressing Cells and Downregulates Signaling |
title_full_unstemmed | GM1 Is Cytoprotective in GPR37-Expressing Cells and Downregulates Signaling |
title_short | GM1 Is Cytoprotective in GPR37-Expressing Cells and Downregulates Signaling |
title_sort | gm1 is cytoprotective in gpr37-expressing cells and downregulates signaling |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657933/ https://www.ncbi.nlm.nih.gov/pubmed/34884663 http://dx.doi.org/10.3390/ijms222312859 |
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