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Dev Cell. 2017 May 22;41(4):424-437.e4. doi: 10.1016/j.devcel.2017.04.013.

Dephosphorylation of the Ndc80 Tail Stabilizes Kinetochore-Microtubule Attachments via the Ska Complex.

Author information

1
Ludwig Institute for Cancer Research, CMM-E Room 3052, 9500 Gilman Drive, La Jolla, CA 92093-0653, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: dcheerambathur@ucsd.edu.
2
Ludwig Institute for Cancer Research, CMM-E Room 3052, 9500 Gilman Drive, La Jolla, CA 92093-0653, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
3
Department of Biological Sciences, Butler University, 4600 Sunset Boulevard, Indianapolis, IN 46208, USA.
4
Ludwig Institute for Cancer Research, CMM-E Room 3052, 9500 Gilman Drive, La Jolla, CA 92093-0653, USA; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: abdesai@ucsd.edu.

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.

KEYWORDS:

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

PMID:
28535376
PMCID:
PMC5572820
DOI:
10.1016/j.devcel.2017.04.013
[Indexed for MEDLINE]
Free PMC Article

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