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Nat Cell Biol. 2018 Jul;20(7):800-810. doi: 10.1038/s41556-018-0130-3. Epub 2018 Jun 18.

Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis.

Author information

1
Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.
2
Department of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
4
Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
5
Biocomputing Unit, National Center for Biotechnology (CSIC), Darwin 3, Campus Universidad Autónoma, Madrid, Spain.
6
Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Universitätsstraße, Essen, Germany.
7
Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands. g.kops@hubrecht.eu.

Abstract

Faithful chromosome segregation depends on the ability of sister kinetochores to attach to spindle microtubules. The outer layer of kinetochores transiently expands in early mitosis to form a fibrous corona, and compacts following microtubule capture. Here we show that the dynein adaptor Spindly and the RZZ (ROD-Zwilch-ZW10) complex drive kinetochore expansion in a dynein-independent manner. C-terminal farnesylation and MPS1 kinase activity cause conformational changes of Spindly that promote oligomerization of RZZ-Spindly complexes into a filamentous meshwork in cells and in vitro. Concurrent with kinetochore expansion, Spindly potentiates kinetochore compaction by recruiting dynein via three conserved short linear motifs. Expanded kinetochores unable to compact engage in extensive, long-lived lateral microtubule interactions that persist to metaphase, and result in merotelic attachments and chromosome segregation errors in anaphase. Thus, dynamic kinetochore size regulation in mitosis is coordinated by a single, Spindly-based mechanism that promotes initial microtubule capture and subsequent correct maturation of attachments.

PMID:
29915359
PMCID:
PMC6485389
DOI:
10.1038/s41556-018-0130-3
[Indexed for MEDLINE]
Free PMC Article

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