The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle bipolarity

Nat Cell Biol. 2006 Oct;8(10):1095-101. doi: 10.1038/ncb1474. Epub 2006 Sep 17.

Abstract

Formation of a bipolar spindle is essential for faithful chromosome segregation at mitosis. Because centrosomes define spindle poles, defects in centrosome number and structural organization can lead to a loss of bipolarity. In addition, microtubule-mediated pulling and pushing forces acting on centrosomes and chromosomes are also important for bipolar spindle formation. Polo-like kinase 1 (Plk1) is a highly conserved Ser/Thr kinase that has essential roles in the formation of a bipolar spindle with focused poles. However, the mechanism by which Plk1 regulates spindle-pole formation is poorly understood. Here, we identify a novel centrosomal substrate of Plk1, Kizuna (Kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles. We demonstrate that Kiz is critical for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation, and suggest that Plk1 maintains the integrity of the spindle poles by phosphorylating Kiz.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / physiology*
  • Cell Nucleus
  • Centrosome*
  • HeLa Cells
  • Humans
  • Lim Kinases
  • Mitosis*
  • Phosphorylation
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / physiology*
  • S Phase
  • Spindle Apparatus*

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Protein Kinases
  • LIMK1 protein, human
  • Lim Kinases
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1