Abstract
ABSTRACTCilia are extended from mother centrioles in quiescent G0/G1 cells and retracted in dividing cells. Diverse post-translational modifications play roles in the assembly and disassembly of the cilium. Here, we examined class I histone deacetylases (HDACs) as positive regulators of cilia assembly in serum-deprived RPE1 and HK2 cells. We observed that the number of cells with cilia was significantly reduced in HDAC3- and HDAC8-depleted cells. The ciliary length also decreased in HDAC3- and HDAC8-depleted cells compared to that in control cells. A knockdown-rescue experiment showed that wild-type HDAC3 and HDAC8 rescued the cilia assembly and ciliary length in HDAC3- and HDAC8-depleted cells, respectively; however, deacetylase-dead HDAC3 and HDAC8 mutants did not. This suggests that deacetylase activity is critical for both HDAC3 and HDAC8 function in cilia assembly and ciliary length control. This is the first study to report that HDACs are required for the assembly and elongation of the primary cilia.
Highlights
The primary cilium is a non-motile, sensory organelle that protrudes from the cell surface
The ciliary length was shortened following treatment with 300 nM or higher concentrations of trichostatin A (TSA) (Fig. 1C). These results suggest that class I histone deacetylases (HDACs) are required for the assembly and elongation of the cilia because the enzymatic activities of class I HDACs were almost completely inhibited by 300 nM TSA
The depletion of HDAC3 and HDAC8 significantly reduced the number of cells with cilia in both the RPE1 and HK2 cells compared to those in the corresponding control cells (Fig. 2A,B)
Summary
The primary cilium is a non-motile, sensory organelle that protrudes from the cell surface. It transduces specific intercellular signals to the cell body and regulates various cellular events for growth and differentiation. The primary cilium originates from a mother centriole in a quiescent G0/G1 cell. The first visible sign of ciliogenesis may be the accumulation of Golgi-derived ciliary vesicles in the vicinity of distal appendages of mother centrioles (Sánchez and Dynlacht, 2016). Vesicular fusion produces a membranous cap on the distal tip of the mother centriole. The mother centriole differentiates into a basal body and extends microtubules underneath the cap. The nascent cilium docks at the cytoplasmic membrane by fusion with the ciliary sheath, establishing the continuity of these compartments (Sung and Leroux, 2013). Tubulin deacetylation precedes regression of the ciliary axoneme (Li and Yang, 2015)
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