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Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila
Adenosine (Ado) is an important signaling molecule involved in stress responses. Studies in mammalian models have shown that Ado regulates signaling mechanisms involved in “danger-sensing” and tissue-protection. Yet, little is known about the role of Ado signaling in Drosophila. In the present study...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994771/ https://www.ncbi.nlm.nih.gov/pubmed/33777958 http://dx.doi.org/10.3389/fcell.2021.651367 |
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author | Lin, Yu-Hsien Maaroufi, Houda Ouns Kucerova, Lucie Rouhova, Lenka Filip, Tomas Zurovec, Michal |
author_facet | Lin, Yu-Hsien Maaroufi, Houda Ouns Kucerova, Lucie Rouhova, Lenka Filip, Tomas Zurovec, Michal |
author_sort | Lin, Yu-Hsien |
collection | PubMed |
description | Adenosine (Ado) is an important signaling molecule involved in stress responses. Studies in mammalian models have shown that Ado regulates signaling mechanisms involved in “danger-sensing” and tissue-protection. Yet, little is known about the role of Ado signaling in Drosophila. In the present study, we observed lower extracellular Ado concentration and suppressed expression of Ado transporters in flies expressing mutant huntingtin protein (mHTT). We altered Ado signaling using genetic tools and found that the overexpression of Ado metabolic enzymes, as well as the suppression of Ado receptor (AdoR) and transporters (ENTs), were able to minimize mHTT-induced mortality. We also identified the downstream targets of the AdoR pathway, the modifier of mdg4 (Mod(mdg4)) and heat-shock protein 70 (Hsp70), which modulated the formation of mHTT aggregates. Finally, we showed that a decrease in Ado signaling affects other Drosophila stress reactions, including paraquat and heat-shock treatments. Our study provides important insights into how Ado regulates stress responses in Drosophila. |
format | Online Article Text |
id | pubmed-7994771 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79947712021-03-27 Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila Lin, Yu-Hsien Maaroufi, Houda Ouns Kucerova, Lucie Rouhova, Lenka Filip, Tomas Zurovec, Michal Front Cell Dev Biol Cell and Developmental Biology Adenosine (Ado) is an important signaling molecule involved in stress responses. Studies in mammalian models have shown that Ado regulates signaling mechanisms involved in “danger-sensing” and tissue-protection. Yet, little is known about the role of Ado signaling in Drosophila. In the present study, we observed lower extracellular Ado concentration and suppressed expression of Ado transporters in flies expressing mutant huntingtin protein (mHTT). We altered Ado signaling using genetic tools and found that the overexpression of Ado metabolic enzymes, as well as the suppression of Ado receptor (AdoR) and transporters (ENTs), were able to minimize mHTT-induced mortality. We also identified the downstream targets of the AdoR pathway, the modifier of mdg4 (Mod(mdg4)) and heat-shock protein 70 (Hsp70), which modulated the formation of mHTT aggregates. Finally, we showed that a decrease in Ado signaling affects other Drosophila stress reactions, including paraquat and heat-shock treatments. Our study provides important insights into how Ado regulates stress responses in Drosophila. Frontiers Media S.A. 2021-03-12 /pmc/articles/PMC7994771/ /pubmed/33777958 http://dx.doi.org/10.3389/fcell.2021.651367 Text en Copyright © 2021 Lin, Maaroufi, Kucerova, Rouhova, Filip and Zurovec. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Lin, Yu-Hsien Maaroufi, Houda Ouns Kucerova, Lucie Rouhova, Lenka Filip, Tomas Zurovec, Michal Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila |
title | Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila |
title_full | Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila |
title_fullStr | Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila |
title_full_unstemmed | Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila |
title_short | Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila |
title_sort | adenosine receptor and its downstream targets, mod(mdg4) and hsp70, work as a signaling pathway modulating cytotoxic damage in drosophila |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994771/ https://www.ncbi.nlm.nih.gov/pubmed/33777958 http://dx.doi.org/10.3389/fcell.2021.651367 |
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