Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation.
Roberto QuadriSarah SerticAnna GhilardiDiego RondelliGuido Roberto GalloLuca Del GiaccoMarco Muzi-FalconiPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- cell cycle
- histone deacetylase
- induced apoptosis
- cell cycle arrest
- single cell
- protein kinase
- cell proliferation
- gene expression
- transcription factor
- endothelial cells
- oxidative stress
- mesenchymal stem cells
- genome wide
- escherichia coli
- bone marrow
- high resolution
- mouse model
- cell death
- tandem mass spectrometry
- signaling pathway