Dual detection of chromosomes and microtubules by the chromosomal passenger complex drives spindle assembly.
Chromosome-dependent spindle assembly requires the chromosomal recruitment and activation of Aurora B, the kinase subunit of the chromosomal passenger complex (CPC). It remains unclear how the chromosome-activated kinase spatially transmits signals to organize the micron-scale spindle. Here we reveal that the CPC must detect two structures, chromosomes and microtubules, to support spindle assembly in Xenopus egg extracts. While Aurora B is enriched on chromosomes in metaphase, we establish that a fraction of Aurora B is targeted to the metaphase spindle and phosphorylates microtubule-bound substrates. We demonstrate that chromosomally activated Aurora B must be targeted to microtubules to drive spindle assembly. Moreover, although the CPC-microtubule interaction can activate Aurora B, which further promotes microtubule assembly, this positive feedback is not initiated without chromosomes. We propose that the dual detection of chromosomes and microtubules by the CPC is a critical step in assembling spindles around and only around chromosomes.
Tseng
Boo Shan
BS
Laboratory of Chromosome and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Tan
Lei
L
Kapoor
Tarun M
TM
Funabiki
Hironori
H
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis / Q000502:physiology*; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism; D014982:Xenopus laevis
D002868:Chromosomal Proteins, Non-Histone; C506222:INCENP protein, Xenopus; D046911:Macromolecular Substances; D011108:Polymers; D029867:Xenopus Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases