Data di Pubblicazione:
2021
Citazione:
Phosphorylation of H3-Thr3 by Haspin is required for primary cilia regulation / R. Quadri, S. Sertic, A. Ghilardi, D. Rondelli, G.R. Gallo, L. Del Giacco, M. Muzi-Falconi. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:14(2021 Jul 20), pp. 7753.1-7753.16. [10.3390/ijms22147753]
Abstract:
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 inducerobliterator 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Haspin; primary cilia; Dido3; HDAC6; ciliopathy; H3T3; zebrafish
Elenco autori:
R. Quadri, S. Sertic, A. Ghilardi, D. Rondelli, G.R. Gallo, L. Del Giacco, M. Muzi-Falconi
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