Loss of CENP-F results in distinct microtubule-related defects without chromosomal abnormalities

Mol Biol Cell. 2016 Jul 1;27(13):1990-9. doi: 10.1091/mbc.E15-12-0848. Epub 2016 May 4.

Abstract

Microtubule (MT)-binding centromere protein F (CENP-F) was previously shown to play a role exclusively in chromosome segregation during cellular division. Many cell models of CENP-F depletion show a lag in the cell cycle and aneuploidy. Here, using our novel genetic deletion model, we show that CENP-F also regulates a broader range of cellular functions outside of cell division. We characterized CENP-F(+/+) and CENP-F(-/-) mouse embryonic fibroblasts (MEFs) and found drastic differences in multiple cellular functions during interphase, including cell migration, focal adhesion dynamics, and primary cilia formation. We discovered that CENP-F(-/-) MEFs have severely diminished MT dynamics, which underlies the phenotypes we describe. These data, combined with recent biochemical research demonstrating the strong binding of CENP-F to the MT network, support the conclusion that CENP-F is a powerful regulator of MT dynamics during interphase and affects heterogeneous cell functions.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Centromere / metabolism
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Aberrations
  • Chromosome Segregation
  • Fibroblasts
  • Interphase / genetics
  • Kinetochores / metabolism
  • Mice
  • Mice, Knockout
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism*
  • Microtubules / physiology
  • Mitosis / genetics
  • Protein Binding

Substances

  • Chromosomal Proteins, Non-Histone
  • Microfilament Proteins
  • centromere protein F