Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment

Mol Biol Cell. 2019 Apr 15;30(9):1060-1068. doi: 10.1091/mbc.E18-09-0546. Epub 2019 Feb 20.

Abstract

Accurate partitioning of chromosomes during mitosis is essential for genetic stability and requires the assembly of the dynamic mitotic spindle and proper kinetochore-microtubule attachment. The spindle assembly checkpoint (SAC) monitors the incompleteness and errors in kinetochore-microtubule attachment and delays anaphase. The SAC kinase Mps1 regulates the recruitment of downstream effectors to unattached kinetochores. Mps1 also actively promotes chromosome alignment during metaphase, but the underlying mechanism is not completely understood. Here, we show that Mps1 regulates chromosome alignment through MCRS1, a spindle assembly factor that controls the dynamics of the minus end of kinetochore microtubules. Mps1 binds and phosphorylates MCRS1. This mechanism enables KIF2A localization to the minus end of spindle microtubules. Thus, our study reveals a novel role of Mps1 in regulating the dynamics of the minus end of microtubules and expands the functions of Mps1 in genome maintenance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosome Segregation
  • Chromosomes, Human
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • M Phase Cell Cycle Checkpoints
  • Mass Spectrometry / methods
  • Microtubules / metabolism
  • Mitosis / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Cell Cycle Proteins
  • MCRS1 protein, human
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • TTK protein, human