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

Carlos Sacristan, Misbha Ud Din Ahmad, Jenny Keller, Job Fermie, Vincent Groenewold, Eelco Tromer, Alexander Fish, Roberto Melero, José María Carazo, Judith Klumperman, Andrea Musacchio, Anastassis Perrakis, Geert Jpl Kops

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)800-810
Aantal pagina's11
TijdschriftNature Cell Biology
Volume20
Nummer van het tijdschrift7
DOI's
StatusGepubliceerd - jul 2018

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