Cargando…
The importance of serine 776 in Ataxin-1 partner selection: A FRET Analysis
Anomalous expansion of a polymorphic tract in Ataxin-1 causes the autosomal dominant spinocerebellar ataxia type 1. In addition to polyglutamine expansion, requirements for development of pathology are phosphorylation of serine 776 in Ataxin-1 and nuclear localization of the protein. The phosphoryla...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513968/ https://www.ncbi.nlm.nih.gov/pubmed/23213356 http://dx.doi.org/10.1038/srep00919 |
_version_ | 1782251946288087040 |
---|---|
author | Menon, Rajesh P. Soong, Daniel de Chiara, Cesira Holt, Mark R. Anilkumar, Narayana Pastore, Annalisa |
author_facet | Menon, Rajesh P. Soong, Daniel de Chiara, Cesira Holt, Mark R. Anilkumar, Narayana Pastore, Annalisa |
author_sort | Menon, Rajesh P. |
collection | PubMed |
description | Anomalous expansion of a polymorphic tract in Ataxin-1 causes the autosomal dominant spinocerebellar ataxia type 1. In addition to polyglutamine expansion, requirements for development of pathology are phosphorylation of serine 776 in Ataxin-1 and nuclear localization of the protein. The phosphorylation state of serine 776 is also crucial for selection of the Ataxin-1 multiple partners. Here, we have used FRET for an in cell study of the interaction of Ataxin-1 with the spliceosome-associated U2AF65 and the adaptor 14-3-3 proteins. Using wild-type Ataxin-1 and Ser776 mutants to a phosphomimetic aspartate and to alanine, we show that U2AF65 binds Ataxin-1 in a Ser776 phosphorylation independent manner whereas 14-3-3 interacts with phosphorylated wild-type Ataxin-1 but not with the mutants. These results indicate that Ser776 acts as the molecular switch that discriminates between normal and aberrant function and that phosphomimetics is not a generally valid approach whose applicability should be carefully validated. |
format | Online Article Text |
id | pubmed-3513968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-35139682012-12-04 The importance of serine 776 in Ataxin-1 partner selection: A FRET Analysis Menon, Rajesh P. Soong, Daniel de Chiara, Cesira Holt, Mark R. Anilkumar, Narayana Pastore, Annalisa Sci Rep Article Anomalous expansion of a polymorphic tract in Ataxin-1 causes the autosomal dominant spinocerebellar ataxia type 1. In addition to polyglutamine expansion, requirements for development of pathology are phosphorylation of serine 776 in Ataxin-1 and nuclear localization of the protein. The phosphorylation state of serine 776 is also crucial for selection of the Ataxin-1 multiple partners. Here, we have used FRET for an in cell study of the interaction of Ataxin-1 with the spliceosome-associated U2AF65 and the adaptor 14-3-3 proteins. Using wild-type Ataxin-1 and Ser776 mutants to a phosphomimetic aspartate and to alanine, we show that U2AF65 binds Ataxin-1 in a Ser776 phosphorylation independent manner whereas 14-3-3 interacts with phosphorylated wild-type Ataxin-1 but not with the mutants. These results indicate that Ser776 acts as the molecular switch that discriminates between normal and aberrant function and that phosphomimetics is not a generally valid approach whose applicability should be carefully validated. Nature Publishing Group 2012-12-04 /pmc/articles/PMC3513968/ /pubmed/23213356 http://dx.doi.org/10.1038/srep00919 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Menon, Rajesh P. Soong, Daniel de Chiara, Cesira Holt, Mark R. Anilkumar, Narayana Pastore, Annalisa The importance of serine 776 in Ataxin-1 partner selection: A FRET Analysis |
title | The importance of serine 776 in Ataxin-1 partner selection: A FRET Analysis |
title_full | The importance of serine 776 in Ataxin-1 partner selection: A FRET Analysis |
title_fullStr | The importance of serine 776 in Ataxin-1 partner selection: A FRET Analysis |
title_full_unstemmed | The importance of serine 776 in Ataxin-1 partner selection: A FRET Analysis |
title_short | The importance of serine 776 in Ataxin-1 partner selection: A FRET Analysis |
title_sort | importance of serine 776 in ataxin-1 partner selection: a fret analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513968/ https://www.ncbi.nlm.nih.gov/pubmed/23213356 http://dx.doi.org/10.1038/srep00919 |
work_keys_str_mv | AT menonrajeshp theimportanceofserine776inataxin1partnerselectionafretanalysis AT soongdaniel theimportanceofserine776inataxin1partnerselectionafretanalysis AT dechiaracesira theimportanceofserine776inataxin1partnerselectionafretanalysis AT holtmarkr theimportanceofserine776inataxin1partnerselectionafretanalysis AT anilkumarnarayana theimportanceofserine776inataxin1partnerselectionafretanalysis AT pastoreannalisa theimportanceofserine776inataxin1partnerselectionafretanalysis AT menonrajeshp importanceofserine776inataxin1partnerselectionafretanalysis AT soongdaniel importanceofserine776inataxin1partnerselectionafretanalysis AT dechiaracesira importanceofserine776inataxin1partnerselectionafretanalysis AT holtmarkr importanceofserine776inataxin1partnerselectionafretanalysis AT anilkumarnarayana importanceofserine776inataxin1partnerselectionafretanalysis AT pastoreannalisa importanceofserine776inataxin1partnerselectionafretanalysis |