GDP-To-GTP exchange on the microtubule end can contribute to the frequency of catastrophe

Felipe Andrés Piedra, Tae Kim, Emily S. Garza, Elisabeth A. Geyer, Alexander Burns, Xuecheng Ye, Luke M. Rice

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Microtubules are dynamic polymers of αβ-Tubulin that have essential roles in chromosome segregation and organization of the cytoplasm. Catastrophe-the switch from growing to shrinking-occurs when a microtubule loses its stabilizing GTP cap. Recent evidence indicates that the nucleotide on the microtubule end controls how tightly an incoming subunit will be bound (trans-Acting GTP), but most current models do not incorporate this information. We implemented trans-Acting GTP into a computational model for microtubule dynamics. In simulations, growing microtubules often exposed terminal GDP-bound subunits without undergoing catastrophe. Transient GDP exposure on the growing plus end slowed elongation by reducing the number of favorable binding sites on the microtubule end. Slower elongation led to erosion of the GTP cap and an increase in the frequency of catastrophe. Allowing GDP-To-GTP exchange on terminal subunits in simulations mitigated these effects. Using mutant αβ-Tubulin or modified GTP, we showed experimentally that a more readily exchangeable nucleotide led to less frequent catastrophe. Current models for microtubule dynamics do not account for GDP-To-GTP exchange on the growing microtubule end, so our findings provide a new way of thinking about the molecular events that initiate catastrophe.

Original languageEnglish (US)
Pages (from-to)3515-3525
Number of pages11
JournalMolecular biology of the cell
Volume27
Issue number22
DOIs
StatePublished - Nov 7 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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