The mitotic spindle protein CKAP2 potently increases formation and stability of microtubules

Elife. 2022 Jan 14:11:e72202. doi: 10.7554/eLife.72202.

Abstract

Cells increase microtubule dynamics to make large rearrangements to their microtubule cytoskeleton during cell division. Changes in microtubule dynamics are essential for the formation and function of the mitotic spindle, and misregulation can lead to aneuploidy and cancer. Using in vitro reconstitution assays we show that the mitotic spindle protein Cytoskeleton-Associated Protein 2 (CKAP2) has a strong effect on nucleation of microtubules by lowering the critical tubulin concentration 100-fold. CKAP2 increases the apparent rate constant ka of microtubule growth by 50-fold and increases microtubule growth rates. In addition, CKAP2 strongly suppresses catastrophes. Our results identify CKAP2 as the most potent microtubule growth factor to date. These finding help explain CKAP2's role as an important spindle protein, proliferation marker, and oncogene.

Keywords: TIRF microscopy; biochemistry; cell biology; chemical biology; microtubule-associated proteins; microtubules; mitotic spindle; none.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism*
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / physiology*
  • Mitosis
  • Spindle Apparatus / chemistry*
  • Tubulin / analysis
  • Tubulin / metabolism

Substances

  • CKAP2 protein, mouse
  • Cytoskeletal Proteins
  • Microtubule-Associated Proteins
  • Tubulin

Grants and funding