The kinase activity of aurora B is required for kinetochore-microtubule interactions during mitosis.
As a component of the "chromosomal passenger protein complex," the aurora B kinase is associated with centromeres during prometaphase and with midzone microtubules during anaphase and is required for both mitosis and cytokinesis. Ablation of aurora B causes defects in both prometaphase chromosomal congression and the spindle checkpoint; however, the mechanisms underlying these defects are unclear. To address this question, we have examined chromosomal movement, spindle organization, and microtubule motor distribution in NRK cells transfected with a kinase-inactive, dominant-negative mutant of aurora B, aurora B(K-R). In cells overexpressing aurora B(K-R) fused with GFP, centromeres moved in a synchronized and predominantly unidirectional manner, as opposed to the independent, bidirectional movement in control cells expressing a similar level of wild-type aurora B-GFP. In addition, most kinetochores became physically separated from spindle microtubules, which appeared as a striking bundle between the spindle poles. These defects were associated with a microtubule-dependent depletion of motor proteins dynein and CENP-E from kinetochores. Our observations suggest that aurora B regulates the association of motor proteins with kinetochores during prometaphase. Interactions of kinetochore motors with microtubules may in turn regulate the organization of microtubules, the movement of prometaphase chromosomes, and the release of the spindle checkpoint.
Murata-Hori
Maki
M
Department of Physiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Wang
Yu-li
YL
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D018386:Kinetochores / Q000502:physiology*; D008164:Luminescent Proteins / Q000378:metabolism; D008845:Microinjections; D008870:Microtubules / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C576925:Aurkb protein, rat; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases