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Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly

Cilia play important roles in sensing extracellular signals and directing fluid flow. Ciliary dysfunction is associated with a variety of diseases known as ciliopathies. Histone deacetylase 6 (HDAC6) has recently emerged as a major driver of ciliary disassembly, but little is known about the downstr...

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Autores principales: Ran, Jie, Yang, Yunfan, Li, Dengwen, Liu, Min, Zhou, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526867/
https://www.ncbi.nlm.nih.gov/pubmed/26246421
http://dx.doi.org/10.1038/srep12917
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author Ran, Jie
Yang, Yunfan
Li, Dengwen
Liu, Min
Zhou, Jun
author_facet Ran, Jie
Yang, Yunfan
Li, Dengwen
Liu, Min
Zhou, Jun
author_sort Ran, Jie
collection PubMed
description Cilia play important roles in sensing extracellular signals and directing fluid flow. Ciliary dysfunction is associated with a variety of diseases known as ciliopathies. Histone deacetylase 6 (HDAC6) has recently emerged as a major driver of ciliary disassembly, but little is known about the downstream players. Here we provide the first evidence that HDAC6-mediated deacetylation of α-tubulin and cortactin is critical for its induction of ciliary disassembly. HDAC6 is localized in the cytoplasm and enriched at the centrosome and basal body. Overexpression of HDAC6 decreases the levels of acetylated α-tubulin and cortactin without affecting the expression or localization of known ciliary regulators. We also find that overexpression of α-tubulin or cortactin or their acetylation-deficient mutants enhances the ability of HDAC6 to induce ciliary disassembly. In addition, acetylation-mimicking mutants of α-tubulin and cortactin counteract HDAC6-induced ciliary disassembly. Furthermore, HDAC6 stimulates actin polymerization, and inhibition of actin polymerization abolishes the activity of HDAC6 to trigger ciliary disassembly. These findings provide mechanistic insight into the ciliary role of HDAC6 and underscore the importance of reversible acetylation in regulating ciliary homeostasis.
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spelling pubmed-45268672015-08-07 Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly Ran, Jie Yang, Yunfan Li, Dengwen Liu, Min Zhou, Jun Sci Rep Article Cilia play important roles in sensing extracellular signals and directing fluid flow. Ciliary dysfunction is associated with a variety of diseases known as ciliopathies. Histone deacetylase 6 (HDAC6) has recently emerged as a major driver of ciliary disassembly, but little is known about the downstream players. Here we provide the first evidence that HDAC6-mediated deacetylation of α-tubulin and cortactin is critical for its induction of ciliary disassembly. HDAC6 is localized in the cytoplasm and enriched at the centrosome and basal body. Overexpression of HDAC6 decreases the levels of acetylated α-tubulin and cortactin without affecting the expression or localization of known ciliary regulators. We also find that overexpression of α-tubulin or cortactin or their acetylation-deficient mutants enhances the ability of HDAC6 to induce ciliary disassembly. In addition, acetylation-mimicking mutants of α-tubulin and cortactin counteract HDAC6-induced ciliary disassembly. Furthermore, HDAC6 stimulates actin polymerization, and inhibition of actin polymerization abolishes the activity of HDAC6 to trigger ciliary disassembly. These findings provide mechanistic insight into the ciliary role of HDAC6 and underscore the importance of reversible acetylation in regulating ciliary homeostasis. Nature Publishing Group 2015-08-06 /pmc/articles/PMC4526867/ /pubmed/26246421 http://dx.doi.org/10.1038/srep12917 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ran, Jie
Yang, Yunfan
Li, Dengwen
Liu, Min
Zhou, Jun
Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly
title Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly
title_full Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly
title_fullStr Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly
title_full_unstemmed Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly
title_short Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly
title_sort deacetylation of α-tubulin and cortactin is required for hdac6 to trigger ciliary disassembly
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526867/
https://www.ncbi.nlm.nih.gov/pubmed/26246421
http://dx.doi.org/10.1038/srep12917
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