Dephosphorylation of the Ndc80 tail stabilizes kinetochore-microtubule attachments via the ska complex

Dhanya K. Cheerambathur, Bram Prevo, Neil Hattersley, Lindsay Lewellyn, Kevin D. Corbett, Karen Oegema, Arshad Desai

Research output: Contribution to journalArticlepeer-review

Abstract

During cell division, genome inheritance is orchestrated by microtubule attachments formed at kinetochores of mitotic chromosomes. The primary microtubule coupler at the kinetochore, the Ndc80 complex, is regulated by Aurora kinase phosphorylation of its N-terminal tail. Dephosphorylation is proposed to stabilize kinetochore-microtubule attachments by strengthening electrostatic interactions of the tail with the microtubule lattice. Here, we show that removal of the Ndc80 tail, which compromises in vitro microtubule binding, has no effect on kinetochore-microtubule attachments in the Caenorhabditis elegans embryo. Despite this, preventing Aurora phosphorylation of the tail results in prematurely stable attachments that restrain spindle elongation. This premature stabilization requires the conserved microtubule-binding Ska complex, which enriches at attachment sites prior to anaphase onset to dampen chromosome motion. We propose that Ndc80-tail dephosphorylation promotes stabilization of kinetochore-microtubule attachments via the Ska complex and that this mechanism ensures accurate segregation by constraining chromosome motion following biorientation on the spindle.

Original languageEnglish
Pages (from-to)424-437.e4
Number of pages18
JournalDevelopmental Cell
Volume41
Issue number4
DOIs
Publication statusPublished - 22 May 2017

Keywords

  • cell division
  • cell polarity
  • centromere
  • chromosome segregation
  • kinetochore
  • microtubule
  • mitosis
  • Ndc80 complex
  • Ska complex

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