Suppression of microtubule assembly kinetics by the mitotic protein TPX2

Taylor A. Reid, Breanna M. Schuster, Barbara J. Mann, Sai Keshavan Balchand, Melissa Plooster, Mark McClellan, Courtney E. Coombes, Pat Wadsworth, Melissa K. Gardner

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

TPX2 is a widely conserved microtubule-associated protein that is required for mitotic spindle formation and function. Previous studies have demonstrated that TPX2 is required for the nucleation of microtubules around chromosomes; however, the molecular mechanism by which TPX2 promotes microtubule nucleation remains a mystery. In this study, we found that TPX2 acts to suppress tubulin subunit off-rates during microtubule assembly and disassembly, thus allowing for the support of unprecedentedly slow rates of plus-end microtubule growth, and also leading to a dramatically reduced microtubule shortening rate. These changes in microtubule dynamics can be explained in computational simulations by a moderate increase in tubulin-tubulin bond strength upon TPX2 association with the microtubule lattice, which in turn acts to reduce the departure rate of tubulin subunits from the microtubule ends. Thus, the direct suppression of tubulin subunit off-rates by TPX2 during microtubule growth and shortening could provide a molecular mechanism to explain the nucleation of new microtubules in the presence of TPX2.

Original languageEnglish (US)
Pages (from-to)1319-1328
Number of pages10
JournalJournal of cell science
Volume129
Issue number7
DOIs
StatePublished - Apr 1 2016

Bibliographical note

Publisher Copyright:
© 2016. Published by The Company of Biologists Ltd | Journal of Cell Science.

Keywords

  • Dynamic instability
  • Microtubule
  • Microtubule-associated protein
  • Mitosis

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