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Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation
A role for the cytoplasmic protein synphilin-1 in regulating energy balance has been demonstrated recently. Expression of synphilin-1 increases ATP levels in cultured cells. However, the mechanism by which synphilin-1 alters cellular energy status is unknown. Here, we used cell models and biochemica...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352261/ https://www.ncbi.nlm.nih.gov/pubmed/32570982 http://dx.doi.org/10.3390/ijms21124352 |
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author | Li, Tianxia Liu, Jingnan Guo, Gongbo Ning, Bo Li, Xueping Zhu, Guangjing Yang, Dejun Moran, Timothy H. Smith, Wanli W. |
author_facet | Li, Tianxia Liu, Jingnan Guo, Gongbo Ning, Bo Li, Xueping Zhu, Guangjing Yang, Dejun Moran, Timothy H. Smith, Wanli W. |
author_sort | Li, Tianxia |
collection | PubMed |
description | A role for the cytoplasmic protein synphilin-1 in regulating energy balance has been demonstrated recently. Expression of synphilin-1 increases ATP levels in cultured cells. However, the mechanism by which synphilin-1 alters cellular energy status is unknown. Here, we used cell models and biochemical approaches to investigate the cellular functions of synphilin-1 on the AMP-activated protein kinase (AMPK) signaling pathway, which may affect energy balance. Overexpression of synphilin-1 increased AMPK phosphorylation (activation). Moreover, synphilin-1 interacted with AMPK by co-immunoprecipitation and GST (glutathione S-transferase) pull-down assays. Knockdown of synphilin-1 reduced AMPK phosphorylation. Overexpression of synphilin-1 also altered AMPK downstream signaling, i.e., a decrease in acetyl CoA carboxylase (ACC) phosphorylation, and an increase in p70S6K phosphorylation. Treatment of compound C (an AMPK inhibitor) reduced synphilin-1 binding with AMPK. In addition, compound C diminished synphilin-1-induced AMPK phosphorylation, and the increase in cellular ATP (adenosine triphosphate) levels. Our results demonstrated that synphilin-1 couples with AMPK, and they exert mutual effects on each other to regulate cellular energy status. These findings not only identify novel cellular actions of synphilin-1, but also provide new insights into the roles of synphilin-1 in regulating energy currency, ATP. |
format | Online Article Text |
id | pubmed-7352261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73522612020-07-21 Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation Li, Tianxia Liu, Jingnan Guo, Gongbo Ning, Bo Li, Xueping Zhu, Guangjing Yang, Dejun Moran, Timothy H. Smith, Wanli W. Int J Mol Sci Article A role for the cytoplasmic protein synphilin-1 in regulating energy balance has been demonstrated recently. Expression of synphilin-1 increases ATP levels in cultured cells. However, the mechanism by which synphilin-1 alters cellular energy status is unknown. Here, we used cell models and biochemical approaches to investigate the cellular functions of synphilin-1 on the AMP-activated protein kinase (AMPK) signaling pathway, which may affect energy balance. Overexpression of synphilin-1 increased AMPK phosphorylation (activation). Moreover, synphilin-1 interacted with AMPK by co-immunoprecipitation and GST (glutathione S-transferase) pull-down assays. Knockdown of synphilin-1 reduced AMPK phosphorylation. Overexpression of synphilin-1 also altered AMPK downstream signaling, i.e., a decrease in acetyl CoA carboxylase (ACC) phosphorylation, and an increase in p70S6K phosphorylation. Treatment of compound C (an AMPK inhibitor) reduced synphilin-1 binding with AMPK. In addition, compound C diminished synphilin-1-induced AMPK phosphorylation, and the increase in cellular ATP (adenosine triphosphate) levels. Our results demonstrated that synphilin-1 couples with AMPK, and they exert mutual effects on each other to regulate cellular energy status. These findings not only identify novel cellular actions of synphilin-1, but also provide new insights into the roles of synphilin-1 in regulating energy currency, ATP. MDPI 2020-06-18 /pmc/articles/PMC7352261/ /pubmed/32570982 http://dx.doi.org/10.3390/ijms21124352 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Tianxia Liu, Jingnan Guo, Gongbo Ning, Bo Li, Xueping Zhu, Guangjing Yang, Dejun Moran, Timothy H. Smith, Wanli W. Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation |
title | Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation |
title_full | Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation |
title_fullStr | Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation |
title_full_unstemmed | Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation |
title_short | Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation |
title_sort | synphilin-1 interacts with ampk and increases ampk phosphorylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352261/ https://www.ncbi.nlm.nih.gov/pubmed/32570982 http://dx.doi.org/10.3390/ijms21124352 |
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