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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

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Kinetochore-bound Mps1 regulates kinetochore-microtubule attachments via Ndc80 phosphorylation

Krishna K Sarangapani1, Lori B Koch2,3,4, Christian R Nelson2,3

  • 1Department of Physiology & Biophysics, University of Washington, Seattle, WA.

The Journal of Cell Biology
|October 14, 2021
PubMed

Insights

The Mps1 kinase weakens incorrect kinetochore-microtubule attachments by phosphorylating Ndc80, aiding cell division error correction. This complements the known role of Aurora B kinase in ensuring accurate chromosome segregation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cell division relies on accurate kinetochore-microtubule attachments to prevent chromosome missegregation.
  • Aurora B kinase is known to correct erroneous attachments by phosphorylating microtubule-binding proteins.
  • The role of Mps1 kinase in error correction remains less understood.

Purpose of the Study:

  • To investigate the specific role of Mps1 kinase in correcting kinetochore-microtubule attachment errors.
  • To differentiate the functions of Mps1 from Aurora B kinase in this process.

Main Methods:

  • Utilized a reconstitution-based approach to isolate Mps1 activity.
  • Activated endogenous Mps1 in vitro with purified kinetochores.
  • Analyzed the effects of Mps1 phosphorylation on Ndc80, a key microtubule-binding protein.
  • Examined genetic interactions and segregation defects in phospho-deficient Ndc80 mutants.

Main Results:

  • Activated Mps1 kinase weakens kinetochore-microtubule attachments through Ndc80 phosphorylation.
  • Mps1-mediated Ndc80 phosphorylation is crucial for error correction, as indicated by genetic interactions.
  • Mps1 activity is enhanced on kinetochores experiencing low tension.
  • Mps1 phosphorylation of Ndc80 is stimulated on kinetochores lacking tension.

Conclusions:

  • Mps1 kinase provides an additional mechanism for correcting erroneous kinetochore-microtubule attachments.
  • Mps1 activity complements the established error correction function of Aurora B kinase.
  • These findings enhance our understanding of the molecular machinery ensuring faithful chromosome segregation during mitosis.

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