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 hi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5176320?pdf=render |
| _version_ | 1818244965136859136 |
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| author | Andrew W Hwang Hanna Trzeciakiewicz Dave Friedmann Chao-Xing Yuan Ronen Marmorstein Virginia M Y Lee Todd J Cohen |
| author_facet | Andrew W Hwang Hanna Trzeciakiewicz Dave Friedmann Chao-Xing Yuan Ronen Marmorstein Virginia M Y Lee Todd J Cohen |
| author_sort | Andrew W Hwang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T14:25:24Z |
| format | Article |
| id | doaj.art-4fc34fa587d94901880a90f78711b1a7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T14:25:24Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4fc34fa587d94901880a90f78711b1a72022-12-22T00:21:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011112e016891310.1371/journal.pone.0168913Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members.Andrew W HwangHanna TrzeciakiewiczDave FriedmannChao-Xing YuanRonen MarmorsteinVirginia M Y LeeTodd J CohenLysine 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.http://europepmc.org/articles/PMC5176320?pdf=render |
| spellingShingle | Andrew W Hwang Hanna Trzeciakiewicz Dave Friedmann Chao-Xing Yuan Ronen Marmorstein Virginia M Y Lee Todd J Cohen Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC5176320?pdf=render |
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