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Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members
Lysine acetylation has emerged as a dominant post-translational modification (PTM) regulating tau proteins in Alzheimer’s disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule-binding region (MTBR), a region that is highly...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176320/ https://www.ncbi.nlm.nih.gov/pubmed/28002468 http://dx.doi.org/10.1371/journal.pone.0168913 |
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author | Hwang, Andrew W. Trzeciakiewicz, Hanna Friedmann, Dave Yuan, Chao-Xing Marmorstein, Ronen Lee, Virginia M. Y. Cohen, Todd J. |
author_facet | Hwang, Andrew W. Trzeciakiewicz, Hanna Friedmann, Dave Yuan, Chao-Xing Marmorstein, Ronen Lee, Virginia M. Y. Cohen, Todd J. |
author_sort | Hwang, Andrew W. |
collection | PubMed |
description | Lysine acetylation has emerged as a dominant post-translational modification (PTM) regulating tau proteins in Alzheimer’s disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule-binding region (MTBR), a region that is highly conserved among tau, MAP2, and MAP4 family members, implying that acetylation could represent a conserved regulatory mechanism for MAPs beyond tau. Here, we combined mass spectrometry, biochemical assays, and cell-based approaches to demonstrate that the tau family members MAP2 and MAP4 are also subject to reversible acetylation. We identify a cluster of lysines in the MAP2 and MAP4 MTBR that undergo CBP-catalyzed acetylation, many of which are conserved in tau. Similar to tau, MAP2 acetylation can occur in a cysteine-dependent auto-regulatory manner in the presence of acetyl-CoA. Furthermore, tubulin reduced MAP2 acetylation, suggesting tubulin binding dictates MAP acetylation status. Taken together, these results uncover a striking conservation of MAP2/Tau family post-translational modifications that could expand our understanding of the dynamic mechanisms regulating microtubules. |
format | Online Article Text |
id | pubmed-5176320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51763202017-01-04 Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members Hwang, Andrew W. Trzeciakiewicz, Hanna Friedmann, Dave Yuan, Chao-Xing Marmorstein, Ronen Lee, Virginia M. Y. Cohen, Todd J. PLoS One Research Article Lysine acetylation has emerged as a dominant post-translational modification (PTM) regulating tau proteins in Alzheimer’s disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule-binding region (MTBR), a region that is highly conserved among tau, MAP2, and MAP4 family members, implying that acetylation could represent a conserved regulatory mechanism for MAPs beyond tau. Here, we combined mass spectrometry, biochemical assays, and cell-based approaches to demonstrate that the tau family members MAP2 and MAP4 are also subject to reversible acetylation. We identify a cluster of lysines in the MAP2 and MAP4 MTBR that undergo CBP-catalyzed acetylation, many of which are conserved in tau. Similar to tau, MAP2 acetylation can occur in a cysteine-dependent auto-regulatory manner in the presence of acetyl-CoA. Furthermore, tubulin reduced MAP2 acetylation, suggesting tubulin binding dictates MAP acetylation status. Taken together, these results uncover a striking conservation of MAP2/Tau family post-translational modifications that could expand our understanding of the dynamic mechanisms regulating microtubules. Public Library of Science 2016-12-21 /pmc/articles/PMC5176320/ /pubmed/28002468 http://dx.doi.org/10.1371/journal.pone.0168913 Text en © 2016 Hwang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hwang, Andrew W. Trzeciakiewicz, Hanna Friedmann, Dave Yuan, Chao-Xing Marmorstein, Ronen Lee, Virginia M. Y. Cohen, Todd J. Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members |
title | Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members |
title_full | Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members |
title_fullStr | Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members |
title_full_unstemmed | Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members |
title_short | Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members |
title_sort | conserved lysine acetylation within the microtubule-binding domain regulates map2/tau family members |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176320/ https://www.ncbi.nlm.nih.gov/pubmed/28002468 http://dx.doi.org/10.1371/journal.pone.0168913 |
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