Caenorhabditis elegans TLK-1 controls cytokinesis by localizing AIR-2/Aurora B to midzone microtubules.
Defects in chromosome condensation, segregation or cytokinesis during mitosis disrupt genome integrity and cause organismal death or tumorigenesis. The conserved kinase AIR-2/Aurora B is required for normal execution of all these important mitotic events in Caenorhabditis elegans. TLK-1 has been recently shown to be a substrate and activator of AIR-2 in the presence of another AIR-2 activator ICP-1/INCENP, and to cooperate with AIR-2 to ensure proper mitotic chromosome segregation. However, whether TLK-1 may contribute to chromosome condensation or cytokinesis is unclear. A time-lapse microscopy analysis showed that tlk-1 mutants are defective in chromosome condensation and cytokinesis, in addition to chromosome segregation, during mitosis. Our data indicate that TLK-1 contributes to chromosome condensation and segregation, at least in part, in a manner that is distinct from the ICP-1-mediated mechanism and does not involve loading AIR-2 or condensin proteins to mitotic chromosomes. Moreover, TLK-1 functions in cytokinesis by localizing AIR-2 to the midzone microtubules. The localization pattern of TLK-1 is different from those of ICP-1 and AIR-2, revealing differences in dynamic regulation and association of TLK-1 and ICP-1 towards AIR-2 in vivo. Interestingly, human TLK2 could functionally substitute for tlk-1, suggesting that the mitotic roles of TLK members might be evolutionarily conserved.
Yeh
Chan-Hsien
CH
Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.
Yang
Hui-Ju
HJ
Lee
I-Ju
IJ
Wu
Yi-Chun
YC
D000818:Animals; D064107:Aurora Kinase B; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D048749:Cytokinesis; D006801:Humans; D008870:Microtubules / Q000201:enzymology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
D029742:Caenorhabditis elegans Proteins; D011494:Protein Kinases; C498928:TLK-1 protein, C elegans; C121377:protein kinase U; D064107:Aurora Kinase B; D017346:Protein Serine-Threonine Kinases; C491506:air-2 protein, C elegans