Ska1 cooperates with DDA3 for spindle dynamics and spindle attachment to kinetochore

Biochem Biophys Res Commun. 2016 Feb 12;470(3):586-592. doi: 10.1016/j.bbrc.2016.01.101. Epub 2016 Jan 19.

Abstract

Spindle microtubules (MTs) capture kinetochores (KTs) on the centromere sequence of sister chromatids to align at the mitotic equator and segregate toward spindle poles during mitosis. For efficient chromosome capture, KTs initially attach to the lateral surface of a MT, providing a considerably larger contact surface than the MT tip. A sequential change of KT composition upon spindle attachment enables a conversion from lateral to stable end-on attachment. However, the molecular link between spindle dynamics and KT composition is not fully understood. Here, we report that Ska1 and DDA3 act as molecular linkers in the interplay between KTs and spindle dynamics. After recruitment of Kif2a onto the mitotic spindle by DDA3, Ska1 targets Kif2a to the minus-end of spindle MTs and facilitates spindle dynamics. Furthermore, DDA3 targets Ska1 to KTs to stabilize end-on attachment. Thus, our findings identified a definite regulatory mechanism of the search and capture process for stable spindle attachment through cross-talk between spindle dynamics and KT composition mediated by DDA3 and Ska1.

Keywords: DDA3; Kif2a; Ska1; Spindle attachment; Spindle dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomal Proteins, Non-Histone / metabolism*
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Mitosis / physiology*
  • Molecular Motor Proteins / metabolism*
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Spindle Apparatus / physiology*

Substances

  • Chromosomal Proteins, Non-Histone
  • Molecular Motor Proteins
  • PSRC1 protein, human
  • Phosphoproteins
  • SKA1 protein, human