Mar 25, 2016

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

BioRxiv : the Preprint Server for Biology
Felipe-Andres PiedraLuke M Rice


Microtubules are dynamic polymers of αβ-tubulin that have essential roles in chromosome segregation and organizing 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...Continue Reading

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Mentioned in this Paper

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Mutant Proteins
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