Three interacting regions of the Ndc80 and Dam1 complexes support microtubule tip-coupling under load

J Cell Biol. 2022 May 2;221(5):e202107016. doi: 10.1083/jcb.202107016. Epub 2022 Mar 30.

Abstract

Accurate mitosis requires kinetochores to make persistent, load-bearing attachments to dynamic microtubule tips, thereby coupling chromosome movements to tip growth and shortening. This tip-coupling behavior depends on the conserved Ndc80 complex and, in budding yeast, on the Dam1 complex, which bind each other directly via three distinct interacting regions. The functional relevance of these multiple interactions was mysterious. Here we show that interactions between two of these regions support the high rupture strengths that occur when applied force is rapidly increased and also support the stability of tip-coupling when force is held constant over longer durations. The contribution of either of these two regions to tip-coupling is reduced by phosphorylation by Aurora B kinase. The third interaction region makes no apparent contribution to rupture strength, but its phosphorylation by Aurora B kinase specifically decreases the long-term stability of tip-coupling. The specific reduction of long-term stability relative to short-term strength might have important implications for mitotic error correction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism
  • Cell Cycle Proteins
  • Chromosome Segregation
  • Kinetochores* / metabolism
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Microtubules* / metabolism
  • Mitosis*
  • Nuclear Proteins
  • Phosphorylation
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism

Substances

  • Cell Cycle Proteins
  • DAM1 protein, S cerevisiae
  • Microtubule-Associated Proteins
  • NDC80 protein, S cerevisiae
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Aurora Kinase B