Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis

Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centrioles duplicate once per cell cycle, and duplication is coordinated by Polo-like kinase 4 (Plk4). We previously demonstrated that Plk4 accumulation is autoregulated by its own kinase activity. However, loss of heterozygosity of Plk4 in mouse embryonic fibroblasts has been proposed to cause cytokinesis failure as a primary event, leading to centrosome amplification and gross chromosomal abnormalities. Using targeted gene disruption, we show that human epithelial cells with one inactivated Plk4 allele undergo neither cytokinesis failure nor increase in centrosome amplification. Plk4 is shown to localize exclusively at the centrosome, with none in the spindle midbody. Substantial depletion of Plk4 by small interfering RNA leads to loss of centrioles and subsequent spindle defects that lead to a modest increase in the rate of cytokinesis failure. Therefore, Plk4 is a centriole-localized kinase that does not directly regulate cytokinesis.

Keywords

Animals Cell Line Centrioles Centrosome Fibroblasts Gene Knockdown Techniques Heterozygote Humans Mice Microtubules Phenotype Protein Transport Protein-Serine-Threonine Kinases RNA Interference Spindle Apparatus Time-Lapse Imaging Cytokinesis

URI

http://hdl.handle.net/10400.7/634

Citation

Andrew J. Holland, Daniele Fachinetti, Sandrine Da Cruz, Quan Zhu, Benjamin Vitre, Mariana Lince-Faria, Denaly Chen, Nicole Parish, Inder M. Verma, Monica Bettencourt-Dias, and Don W. Cleveland Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis Mol. Biol. Cell 2012 23:10 1838-1845; First Published on March 28, 2012; doi:10.1091/mbc.E11-12-1043