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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...

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Autores principales: Hwang, Andrew W., Trzeciakiewicz, Hanna, Friedmann, Dave, Yuan, Chao-Xing, Marmorstein, Ronen, Lee, Virginia M. Y., Cohen, Todd J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
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.
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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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