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Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation

Primary cilia are commonly found on most quiescent, terminally differentiated cells and play a major role in the regulation of the cell cycle, cell motility, sensing, and cell–cell communication. Alterations in ciliogenesis and cilia maintenance are causative of several human diseases, collectively...

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Autores principales: Quadri, Roberto, Sertic, Sarah, Ghilardi, Anna, Rondelli, Diego, Gallo, Guido Roberto, Del Giacco, Luca, Muzi-Falconi, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307231/
https://www.ncbi.nlm.nih.gov/pubmed/34299370
http://dx.doi.org/10.3390/ijms22147753
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author Quadri, Roberto
Sertic, Sarah
Ghilardi, Anna
Rondelli, Diego
Gallo, Guido Roberto
Del Giacco, Luca
Muzi-Falconi, Marco
author_facet Quadri, Roberto
Sertic, Sarah
Ghilardi, Anna
Rondelli, Diego
Gallo, Guido Roberto
Del Giacco, Luca
Muzi-Falconi, Marco
author_sort Quadri, Roberto
collection PubMed
description Primary cilia are commonly found on most quiescent, terminally differentiated cells and play a major role in the regulation of the cell cycle, cell motility, sensing, and cell–cell communication. Alterations in ciliogenesis and cilia maintenance are causative of several human diseases, collectively known as ciliopathies. A key determinant of primary cilia is the histone deacetylase HDAC6, which regulates their length and resorption and whose distribution is regulated by the death inducer-obliterator 3 (Dido3). Here, we report that the atypical protein kinase Haspin is a key regulator of cilia dynamics. Cells defective in Haspin activity exhibit longer primary cilia and a strong delay in cilia resorption upon cell cycle reentry. We show that Haspin is active in quiescent cells, where it phosphorylates threonine 3 of histone H3, a known mitotic Haspin substrate. Forcing Dido3 detachment from the chromatin prevents Haspin inhibition from impacting cilia dynamics, suggesting that Haspin activity is required for the relocalization of Dido3–HDAC6 to the basal body. Exploiting the zebrafish model, we confirmed the physiological relevance of this mechanism. Our observations shed light on a novel player, Haspin, in the mechanisms that govern the determination of cilia length and the homeostasis of mature cilia.
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spelling pubmed-83072312021-07-25 Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation Quadri, Roberto Sertic, Sarah Ghilardi, Anna Rondelli, Diego Gallo, Guido Roberto Del Giacco, Luca Muzi-Falconi, Marco Int J Mol Sci Article Primary cilia are commonly found on most quiescent, terminally differentiated cells and play a major role in the regulation of the cell cycle, cell motility, sensing, and cell–cell communication. Alterations in ciliogenesis and cilia maintenance are causative of several human diseases, collectively known as ciliopathies. A key determinant of primary cilia is the histone deacetylase HDAC6, which regulates their length and resorption and whose distribution is regulated by the death inducer-obliterator 3 (Dido3). Here, we report that the atypical protein kinase Haspin is a key regulator of cilia dynamics. Cells defective in Haspin activity exhibit longer primary cilia and a strong delay in cilia resorption upon cell cycle reentry. We show that Haspin is active in quiescent cells, where it phosphorylates threonine 3 of histone H3, a known mitotic Haspin substrate. Forcing Dido3 detachment from the chromatin prevents Haspin inhibition from impacting cilia dynamics, suggesting that Haspin activity is required for the relocalization of Dido3–HDAC6 to the basal body. Exploiting the zebrafish model, we confirmed the physiological relevance of this mechanism. Our observations shed light on a novel player, Haspin, in the mechanisms that govern the determination of cilia length and the homeostasis of mature cilia. MDPI 2021-07-20 /pmc/articles/PMC8307231/ /pubmed/34299370 http://dx.doi.org/10.3390/ijms22147753 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Quadri, Roberto
Sertic, Sarah
Ghilardi, Anna
Rondelli, Diego
Gallo, Guido Roberto
Del Giacco, Luca
Muzi-Falconi, Marco
Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation
title Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation
title_full Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation
title_fullStr Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation
title_full_unstemmed Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation
title_short Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation
title_sort phosphorylation of h3-thr3 by haspin is required for primary cilia regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307231/
https://www.ncbi.nlm.nih.gov/pubmed/34299370
http://dx.doi.org/10.3390/ijms22147753
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