TY - JOUR
T1 - Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis
AU - Holland, Andrew J.
AU - Fachinetti, Daniele
AU - Da Cruz, Sandrine
AU - Zhu, Quan
AU - Vitre, Benjamin
AU - Lince-Faria, Mariana
AU - Chen, Denaly
AU - Parish, Nicole
AU - Verma, Inder M.
AU - Bettencourt-Dias, Monica
AU - Cleveland, Don W.
PY - 2012/5/15
Y1 - 2012/5/15
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.E11-12-1043
DO - 10.1091/mbc.E11-12-1043
M3 - Article
C2 - 22456511
AN - SCOPUS:84861163747
SN - 1059-1524
VL - 23
SP - 1838
EP - 1845
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 10
ER -