Microtubule dynamic instability: A new model with coupled GTP hydrolysis and multistep catastrophe

Abstract

A key question in understanding microtubule dynamics is how GTP hydrolysis leads to catastrophe, the switch from slow growth to rapid shrinkage. We first provide a review of the experimental and modeling literature, and then present a new model of microtubule dynamics. We demonstrate that vectorial, random, and coupled hydrolysis mechanisms are not consistent with the dependence of catastrophe on tubulin concentration and show that, although single-protofilament models can explain many features of dynamics, they do not describe catastrophe as a multistep process. Finally, we present a new combined (coupled plus random hydrolysis) multiple-protofilament model that is a simple, analytically solvable generalization of a single-protofilament model. This model accounts for the observed lifetimes of growing microtubules, the delay to catastrophe following dilution and describes catastrophe as a multistep process.

Microtubule catastrophe from protofilament dynamics

“…Although microtubule catastrophes are regularly observed both in vitro and in vivo, there is still some lack of clarity about the sequence of events in a growing microtubule that ultimately leads to its transition to shrinking state (see [23] for a recent review). It has been shown experimentally, first by Odde et al [24] and more recently by Stepanova et al [25] and Gardner et al [26] that microtubule catastrophes have a certain historydependence, i.e., the probability for a microtubule to undergo catastrophe appears to depend on how long its has been growing.…”

Patterning of plant cell wall deposition by cortical microtubules

“…1.3). Dynamic instability emerges from the mechanism of microtubule polymerization 29,30 . Newly added tubulin heterodimers contain GTP which stabilizes the plus end of a microtubule, over time the GTP hydrolyses into GDP which cannot stabilize the microtubule and thus a catastrophe will follow 29,30 .…”

“…Dynamic instability emerges from the mechanism of microtubule polymerization 29,30 . Newly added tubulin heterodimers contain GTP which stabilizes the plus end of a microtubule, over time the GTP hydrolyses into GDP which cannot stabilize the microtubule and thus a catastrophe will follow 29,30 . As long as the rate of polymerization is faster than the GTP hydrolysis, a GTP-cap remains at the plus end of the microtubule preventing a catastrophe 29,30 .…”

Microtubule: a dynamically unstable stochastic phase switching polymer

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