Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates.
Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi-orientation). Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bi-oriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer-based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bi-oriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.
Liu
Dan
D
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Vader
Gerben
G
Vromans
Martijn J M
MJ
Lampson
Michael A
MA
Lens
Susanne M A
SM
D064107:Aurora Kinase B; D064127:Aurora Kinases; D001324:Autoantigens / Q000378:metabolism; D015374:Biosensing Techniques; D045744:Cell Line, Tumor; D002503:Centromere / Q000201:enzymology / Q000378:metabolism*; D000076247:Centromere Protein A; D002842:Chromatids / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
D001324:Autoantigens; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D011993:Recombinant Fusion Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases