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. Author manuscript; available in PMC: 2020 Jun 1.
Published in final edited form as: Curr Opin Cell Biol. 2019 Jan 23;58:34–41. doi: 10.1016/j.ceb.2018.12.007

Figure 4. Models: substrate masking by microtubules and treadmill-removal of Aurora B.

Figure 4.

A. Unattached kinetochore. Centromeric CPC enrichment activates Aurora B through autophosphorylation. Diffusion allows activated Aurora B (red) to access kinetochore substrates (orange dotted arrow), while its reaction is counteracted by PP2A at the kinetochore. The positively charged N-terminal tail of the Ndc80/Hec1 subunit of the Ndc80 complex (green) is recognized by Aurora B and microtubules. In the absence microtubules, Aurora B activated at the centromere can phosphorylate Ndc80.

B. Kinetochore attached to shrinking microtubule ends. The kinetochore is moving to a pole, and is under reduced tension. In the attached kinetochore, microtubules and Aurora B may compete to interact with the Ndc80 N-terminus, necessitating the microtubule-binding capacity of the CPC for effective Ndc80 phosphorylation (substrate masking by microtubules). The majority of the CPC with high Cdk1-dependent phosphorylation on INCENP (shown as orange circles) cannot bind to microtubules, but a small fraction of the CPC with reduced phosphorylation can bind to microtubules for a limited timeframe, during which Aurora B is activated. At the same duration, CPC with activated Aurora B comes closer to kinetochore substrates by treadmilling due to plus-end depolymerization, or stays close to the kinetochore (in the case of taxol-stabilized microtubules), facilitating accessibility of active Aurora B to its kinetochore substrates.

C. Kinetochore attached to growing microtubule ends. The kinetochore is moving away from a pole, and is under tension. The CPC with inactive Aurora B can be activated upon microtubule binding, but by the time when Aurora B is activated, it will already have been treadmilled away from the kinetochore, reducing its accessibility to kinetochore substrates (treadmill-removal). The CPC activated by microtubules or the centromeric chromatin may diffuse into the cytoplasm, but the high Cdk1 activity limits the rebinding to microtubules within the kinetochore.