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Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease
Microtubules (MTs) support a variety of neuronal functions, such as maintenance of cell structure, transport, and synaptic plasticity. Neuronal MTs are highly heterogeneous due to several tubulin isotypes and the presence of multiple post-translational modifications, such as detyrosination and acety...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459041/ https://www.ncbi.nlm.nih.gov/pubmed/36092705 http://dx.doi.org/10.3389/fcell.2022.926914 |
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author | Martínez-Hernández, José Parato, Julie Sharma, Aditi Soleilhac, Jean-Marc Qu, Xiaoyi Tein, Ellen Sproul, Andrew Andrieux, Annie Goldberg, Yves Moutin, Marie-Jo Bartolini, Francesca Peris, Leticia |
author_facet | Martínez-Hernández, José Parato, Julie Sharma, Aditi Soleilhac, Jean-Marc Qu, Xiaoyi Tein, Ellen Sproul, Andrew Andrieux, Annie Goldberg, Yves Moutin, Marie-Jo Bartolini, Francesca Peris, Leticia |
author_sort | Martínez-Hernández, José |
collection | PubMed |
description | Microtubules (MTs) support a variety of neuronal functions, such as maintenance of cell structure, transport, and synaptic plasticity. Neuronal MTs are highly heterogeneous due to several tubulin isotypes and the presence of multiple post-translational modifications, such as detyrosination and acetylation. The tubulin tyrosination/detyrosination cycle is a key player in the maintenance of MT dynamics, as tyrosinated tubulin is associated with more dynamic MTs, while detyrosinated tubulin is linked to longer lived, more stable MTs. Dysfunction of tubulin re-tyrosination was recently correlated to Alzheimer’s disease progression. The implication of tubulin acetylation in Alzheimer’s disease has, however, remained controversial. Here, we demonstrate that tubulin acetylation accumulates in post-mortem brain tissues from Alzheimer’s disease patients and human neurons harboring the Alzheimer’s familial APP-V717I mutation. We further show that tubulin re-tyrosination, which is defective in Alzheimer’s disease, can control acetylated tubulin in primary neurons irrespective of the levels of the enzymes regulating tubulin acetylation, suggesting that reduced MT dynamics associated with impaired tubulin re-tyrosination might contribute to the accumulation of tubulin acetylation that we detected in Alzheimer’s disease. |
format | Online Article Text |
id | pubmed-9459041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94590412022-09-10 Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease Martínez-Hernández, José Parato, Julie Sharma, Aditi Soleilhac, Jean-Marc Qu, Xiaoyi Tein, Ellen Sproul, Andrew Andrieux, Annie Goldberg, Yves Moutin, Marie-Jo Bartolini, Francesca Peris, Leticia Front Cell Dev Biol Cell and Developmental Biology Microtubules (MTs) support a variety of neuronal functions, such as maintenance of cell structure, transport, and synaptic plasticity. Neuronal MTs are highly heterogeneous due to several tubulin isotypes and the presence of multiple post-translational modifications, such as detyrosination and acetylation. The tubulin tyrosination/detyrosination cycle is a key player in the maintenance of MT dynamics, as tyrosinated tubulin is associated with more dynamic MTs, while detyrosinated tubulin is linked to longer lived, more stable MTs. Dysfunction of tubulin re-tyrosination was recently correlated to Alzheimer’s disease progression. The implication of tubulin acetylation in Alzheimer’s disease has, however, remained controversial. Here, we demonstrate that tubulin acetylation accumulates in post-mortem brain tissues from Alzheimer’s disease patients and human neurons harboring the Alzheimer’s familial APP-V717I mutation. We further show that tubulin re-tyrosination, which is defective in Alzheimer’s disease, can control acetylated tubulin in primary neurons irrespective of the levels of the enzymes regulating tubulin acetylation, suggesting that reduced MT dynamics associated with impaired tubulin re-tyrosination might contribute to the accumulation of tubulin acetylation that we detected in Alzheimer’s disease. Frontiers Media S.A. 2022-08-26 /pmc/articles/PMC9459041/ /pubmed/36092705 http://dx.doi.org/10.3389/fcell.2022.926914 Text en Copyright © 2022 Martínez-Hernández, Parato, Sharma, Soleilhac, Qu, Tein, Sproul, Andrieux, Goldberg, Moutin, Bartolini and Peris. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Martínez-Hernández, José Parato, Julie Sharma, Aditi Soleilhac, Jean-Marc Qu, Xiaoyi Tein, Ellen Sproul, Andrew Andrieux, Annie Goldberg, Yves Moutin, Marie-Jo Bartolini, Francesca Peris, Leticia Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease |
title | Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease |
title_full | Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease |
title_fullStr | Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease |
title_full_unstemmed | Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease |
title_short | Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease |
title_sort | crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in alzheimer’s disease |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459041/ https://www.ncbi.nlm.nih.gov/pubmed/36092705 http://dx.doi.org/10.3389/fcell.2022.926914 |
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