A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset

Jeraldine Weber, Thibault Legal, Alicia Perez Lezcano, Agata Gluszek-Kustusz, Calum Paterson, Susana Eibes, Marin Barisic, Owen R. Davies, Julie P.I. Welburn*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

3 Citations (Scopus)
3 Downloads (Pure)

Abstract

The outer corona plays an essential role at the onset of mitosis by expanding to maximize microtubule attachment to kinetochores.1,2 The low-density structure of the corona forms through the expansion of unattached kinetochores. It comprises the RZZ complex, the dynein adaptor Spindly, the plus-end directed microtubule motor centromere protein E (CENP-E), and the Mad1/Mad2 spindle-assembly checkpoint proteins.3,4,5,6,7,8,9,10 CENP-E specifically associates with unattached kinetochores to facilitate chromosome congression,11,12,13,14,15,16 interacting with BubR1 at the kinetochore through its C-terminal region (2091–2358).17,18,19,20,21 We recently showed that CENP-E recruitment to BubR1 at the kinetochores is both rapid and essential for correct chromosome alignment. However, CENP-E is also recruited to the outer corona by a second, slower pathway that is currently undefined.19 Here, we show that BubR1-independent localization of CENP-E is mediated by a conserved loop that is essential for outer-corona targeting. We provide a structural model of the entire CENP-E kinetochore-targeting domain combining X-ray crystallography and Alphafold2. We reveal that maximal recruitment of CENP-E to unattached kinetochores critically depends on BubR1 and the outer corona, including dynein. Ectopic expression of the CENP-E C-terminal domain recruits the RZZ complex, Mad1, and Spindly, and prevents kinetochore biorientation in cells. We propose that BubR1-recruited CENP-E, in addition to its essential role in chromosome alignment to the metaphase plate, contributes to the recruitment of outer corona proteins through interactions with the CENP-E corona-targeting domain to facilitate the rapid capture of microtubules for efficient chromosome alignment and mitotic progression.

Original languageEnglish
JournalCurrent Biology
Volume34
Issue number5
Pages (from-to)1133-1141.e4
Number of pages9
ISSN0960-9822
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Keywords

  • CENP-E motor
  • centromere
  • dynein
  • kinetochore
  • microtubule
  • mitosis
  • motor
  • outer corona
  • prometaphase
  • spindle assembly checkpoint

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