Distinct Roles of the Chromosomal Passenger Complex in the Detection of and Response to Errors in Kinetochore-Microtubule Attachment

Publication date: 25 September 2017
Source:Developmental Cell, Volume 42, Issue 6
Author(s): Julian Haase, Mary Kate Bonner, Hyunmi Halas, Alexander E. Kelly
The chromosomal passenger complex (CPC) localizes to centromeres in early mitosis to activate its subunit Aurora B kinase. However, it is unclear whether centromeric CPC localization contributes to CPC functions beyond Aurora B activation. Here, we show that an activated CPC that cannot localize to centromeres supports functional assembly of the outer kinetochore but is unable to correct errors in kinetochore-microtubule attachment in Xenopus egg extracts. We find that CPC has two distinct roles at centromeres: one to selectively phosphorylate Ndc80 to regulate attachment and a second, conserved kinase-independent role in the proper composition of inner kinetochore proteins. Although a fully assembled inner kinetochore is not required for outer kinetochore assembly, we find it is essential to recruit tension indicators, such as BubR1 and 3F3/2, to erroneous attachments. We conclude centromeric CPC is necessary for tension-dependent removal of erroneous attachments and for the kinetochore composition required to detect tension loss.

Teaser

Error-free chromosome segregation relies on the correction of erroneously attached kinetochore-microtubules by the chromosomal passenger complex (CPC). Haase et al. find centromeric localization of the CPC plays two roles in error correction: one in selectively removing mal-attachments and another in enabling error detection through regulation of inner kinetochore composition.


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