Cdk1-mediated DIAPH1 phosphorylation maintains metaphase cortical tension and inactivates the spindle assembly checkpoint at anaphase

Nat Commun. 2019 Feb 28;10(1):981. doi: 10.1038/s41467-019-08957-w.

Abstract

Animal cells undergo rapid rounding during mitosis, ensuring proper chromosome segregation, during which an outward rounding force abruptly increases upon prometaphase entry and is maintained at a constant level during metaphase. Initial cortical tension is generated by the actomyosin system to which both myosin motors and actin network architecture contribute. However, how cortical tension is maintained and its physiological significance remain unknown. We demonstrate here that Cdk1-mediated phosphorylation of DIAPH1 stably maintains cortical tension after rounding and inactivates the spindle assembly checkpoint (SAC). Cdk1 phosphorylates DIAPH1, preventing profilin1 binding to maintain cortical tension. Mutation of DIAPH1 phosphorylation sites promotes cortical F-actin accumulation, increases cortical tension, and delays anaphase onset due to SAC activation. Measurement of the intra-kinetochore length suggests that Cdk1-mediated cortex relaxation is indispensable for kinetochore stretching. We thus uncovered a previously unknown mechanism by which Cdk1 coordinates cortical tension maintenance and SAC inactivation at anaphase onset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Anaphase / physiology
  • CDC2 Protein Kinase / metabolism*
  • Chromosome Segregation / physiology*
  • Cyclin B1 / metabolism
  • Formins
  • Gene Knockout Techniques
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • M Phase Cell Cycle Checkpoints / physiology*
  • Metaphase / physiology
  • Phosphorylation
  • Profilins / chemistry
  • Profilins / genetics
  • Profilins / metabolism
  • Protein Interaction Domains and Motifs
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • CCNB1 protein, human
  • Cyclin B1
  • DIAPH1 protein, human
  • Formins
  • PFN1 protein, human
  • Profilins
  • Recombinant Proteins
  • CDC2 Protein Kinase
  • CDK1 protein, human