Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex to Ensure Error-Free Chromosome Segregation

John Maciejowski, Hauke Drechsler, Kathrin Grundner-Culemann, Edward R. Ballister, Jose Antonio Rodriguez-Rodriguez, Veronica Rodriguez-Bravo, Mathew J.K. Jones, Emily Foley, Michael A. Lampson, Henrik Daub, Andrew D. McAinsh, Prasad V. Jallepalli

Research output: Contribution to journalArticlepeer-review


The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1’s error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore. Substrate modification was microtubule sensitive and opposed by PP2A-B56 phosphatases that stabilize chromosome-spindle attachment. Consistently, Mps1 inhibition rescued K-fiber stability after depleting PP2A-B56. We also identify the Ska complex as a key effector of Mps1 at the kinetochore-microtubule interface, as mutations that mimic constitutive phosphorylation destabilized K fibers in vivo and reduced the efficiency of the Ska complex's conversion from lattice diffusion to end-coupled microtubule binding in vitro. Our results reveal how Mps1 dynamically modifies kinetochores to correct improper attachments and ensure faithful chromosome segregation.

Original languageEnglish (US)
Pages (from-to)143-156.e6
JournalDevelopmental Cell
Issue number2
StatePublished - Apr 24 2017


  • Mps1
  • Ska complex
  • Ska1
  • kinetochore
  • mass spectrometry
  • microtubule
  • mitosis
  • mitotic spindle
  • phosphorylation
  • protein kinase

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology


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