Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15

J Cell Biol. 2019 Apr 1;218(4):1218-1234. doi: 10.1083/jcb.201806195. Epub 2019 Feb 1.

Abstract

Mitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here, we demonstrate that kinesin-binding protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule binding. Consistent with these effects, the mitotic localizations of KIF18A and KIF15 are altered by overexpression of KBP. Cells depleted of KBP exhibit lagging chromosomes in anaphase, an effect that is recapitulated by KIF15 and KIF18A overexpression. Based on these data, we propose a model in which KBP acts as a protein buffer in mitosis, protecting cells from excessive KIF18A and KIF15 activity to promote accurate chromosome segregation.

Publication types

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

MeSH terms

  • Anaphase*
  • Cell Nucleus / enzymology*
  • Cell Nucleus / genetics
  • Chromosome Segregation*
  • Chromosomes, Human*
  • HeLa Cells
  • Humans
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Retinal Pigment Epithelium / enzymology
  • Signal Transduction

Substances

  • KIF15 protein, human
  • KIFBP protein, human
  • Nerve Tissue Proteins
  • KIF18A protein, human
  • Kinesin