PUBLICATION
Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation
- Authors
- Quadri, R., Sertic, S., Ghilardi, A., Rondelli, D., Gallo, G.R., Del Giacco, L., Muzi-Falconi, M.
- ID
- ZDB-PUB-210728-9
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(14): (Journal)
- Registered Authors
- Del Giacco, Luca, Ghilardi, Anna
- Keywords
- Dido3, H3T3, HDAC6, Haspin, ciliopathy, primary cilia, zebrafish
- MeSH Terms
-
- Animals
- Cell Cycle/physiology
- Cells, Cultured
- Chromatin/metabolism
- Cilia/metabolism*
- HEK293 Cells
- Histones/metabolism*
- Humans
- Intracellular Signaling Peptides and Proteins/metabolism*
- Phosphorylation/physiology*
- Protein Serine-Threonine Kinases/metabolism*
- Threonine/metabolism*
- Zebrafish
- PubMed
- 34299370 Full text @ Int. J. Mol. Sci.
Citation
Quadri, R., Sertic, S., Ghilardi, A., Rondelli, D., Gallo, G.R., Del Giacco, L., Muzi-Falconi, M. (2021) Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation. International Journal of Molecular Sciences. 22(14):.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping