Rxivist logo

GTSE1 tunes microtubule stability for chromosome alignment and segregation through MCAK inhibition

By Shweta Bendre, Arnaud Rondelet, Conrad Hall, Nadine Schmidt, Yu-Chih Lin, Gary J. Brouhard, Alexander W. Bird

Posted 04 Aug 2016
bioRxiv DOI: 10.1101/067827 (published DOI: 10.1083/jcb.201606081)

The dynamic regulation of microtubules during mitosis is critical for accurate chromosome segregation and genome stability. Cancer cell lines with hyperstabilized kinetochore microtubules have increased segregation errors and elevated chromosomal instability (CIN), but the genetic defects responsible remain largely unknown. The microtubule depolymerase MCAK can influence CIN through its impact on microtubule stability, but how its potent activity is controlled in cells remains unclear. Here we show that GTSE1, a protein found overexpressed in aneuploid cancer cell lines and tumours, regulates microtubule stability during mitosis by inhibiting MCAK microtubule depolymerase activity. Cells lacking GTSE1 have defects in chromosome alignment and spindle positioning due to microtubule instability caused by excess MCAK activity. Reducing GTSE1 levels in CIN cancer cell lines reduces chromosome missegregation defects, while artificially inducing GTSE1 levels in chromosomally stable cells elevates chromosome missegregation and CIN. Thus GTSE1 inhibition of MCAK activity regulates the balance of microtubule stability that determines the fidelity of chromosome alignment, segregation, and chromosomal stability.

Download data

  • Downloaded 662 times
  • Download rankings, all-time:
    • Site-wide: 30,767 out of 118,796
    • In cell biology: 1,226 out of 5,447
  • Year to date:
    • Site-wide: 97,474 out of 118,796
  • Since beginning of last month:
    • Site-wide: 112,140 out of 118,796

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)