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

International Journal of Molecular Sciences

Anna Ghilardi¹  Sarah Sertic¹  Luca Del Giacco¹  Marco Muzi-Falconi¹  Guido Roberto Gallo¹  Diego Rondelli¹  Roberto Quadri² 

[1] Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy;Istituto Nazionale di Genetica Molecolare, Via Sforza 35, 20122 Milano, Italy;

关键词: Haspin;    primary cilia;    Dido3;    HDAC6;    ciliopathy;    H3T3;   

DOI  :  10.3390/ijms22147753

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown