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Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration
Alpha synuclein (α-syn) is a central player in neurodegeneration, but the mechanisms triggering its pathology are not fully understood. Here we found that α-syn is a highly efficient substrate for arginyltransferase ATE1 and is arginylated in vivo by a novel mid-chain mechanism that targets the acid...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595787/ https://www.ncbi.nlm.nih.gov/pubmed/28900170 http://dx.doi.org/10.1038/s41598-017-11713-z |
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author | Wang, Junling Han, Xuemei Leu, Nicolae Adrian Sterling, Stephanie Kurosaka, Satoshi Fina, Marie Lee, Virginia M. Dong, Dawei W. Yates, John R. Kashina, Anna |
author_facet | Wang, Junling Han, Xuemei Leu, Nicolae Adrian Sterling, Stephanie Kurosaka, Satoshi Fina, Marie Lee, Virginia M. Dong, Dawei W. Yates, John R. Kashina, Anna |
author_sort | Wang, Junling |
collection | PubMed |
description | Alpha synuclein (α-syn) is a central player in neurodegeneration, but the mechanisms triggering its pathology are not fully understood. Here we found that α-syn is a highly efficient substrate for arginyltransferase ATE1 and is arginylated in vivo by a novel mid-chain mechanism that targets the acidic side chains of E46 and E83. Lack of arginylation leads to increased α-syn aggregation and causes the formation of larger pathological aggregates in neurons, accompanied by impairments in its ability to be cleared via normal degradation pathways. In the mouse brain, lack of arginylation leads to an increase in α-syn’s insoluble fraction, accompanied by behavioral changes characteristic for neurodegenerative pathology. Our data show that lack of arginylation in the brain leads to neurodegeneration, and suggests that α-syn arginylation can be a previously unknown factor that facilitates normal α-syn folding and function in vivo. |
format | Online Article Text |
id | pubmed-5595787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55957872017-09-14 Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration Wang, Junling Han, Xuemei Leu, Nicolae Adrian Sterling, Stephanie Kurosaka, Satoshi Fina, Marie Lee, Virginia M. Dong, Dawei W. Yates, John R. Kashina, Anna Sci Rep Article Alpha synuclein (α-syn) is a central player in neurodegeneration, but the mechanisms triggering its pathology are not fully understood. Here we found that α-syn is a highly efficient substrate for arginyltransferase ATE1 and is arginylated in vivo by a novel mid-chain mechanism that targets the acidic side chains of E46 and E83. Lack of arginylation leads to increased α-syn aggregation and causes the formation of larger pathological aggregates in neurons, accompanied by impairments in its ability to be cleared via normal degradation pathways. In the mouse brain, lack of arginylation leads to an increase in α-syn’s insoluble fraction, accompanied by behavioral changes characteristic for neurodegenerative pathology. Our data show that lack of arginylation in the brain leads to neurodegeneration, and suggests that α-syn arginylation can be a previously unknown factor that facilitates normal α-syn folding and function in vivo. Nature Publishing Group UK 2017-09-12 /pmc/articles/PMC5595787/ /pubmed/28900170 http://dx.doi.org/10.1038/s41598-017-11713-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Junling Han, Xuemei Leu, Nicolae Adrian Sterling, Stephanie Kurosaka, Satoshi Fina, Marie Lee, Virginia M. Dong, Dawei W. Yates, John R. Kashina, Anna Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration |
title | Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration |
title_full | Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration |
title_fullStr | Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration |
title_full_unstemmed | Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration |
title_short | Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration |
title_sort | protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595787/ https://www.ncbi.nlm.nih.gov/pubmed/28900170 http://dx.doi.org/10.1038/s41598-017-11713-z |
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