Microtubule Dynamic Instability and GTP Hydrolysis

Erickson, Harold P.; O’Brien, E. Timothy

doi:10.1146/annurev.bb.21.060192.001045

Cited by 220 publications

(158 citation statements)

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“…Microtubules are dynamic structures, i.e., at polymer mass steady state, individual microtubules are observed growing, depolymerizing, or remaining in a paused or attenuated state, in which no changes in microtubule length are observed (Mitchison and Kirschner, 1984). The dynamics of microtubules are controlled by a number of factors including microtubule-associated proteins (Drechsel et al, 1992;Kowalski and Williams, 1993;Dhamodharan and Wadsworth, 1995;Hamill et al, 1998), catastrophe-promoting proteins (reviewed in Walczak, 2000), motor proteins (reviewed in Hunter and Wordeman, 2000), and the GTPase activity of tubulin (reviewed in Erickson and O'Brien, 1992).…”

Section: Introductionmentioning

confidence: 99%

β-Tubulin C354 Mutations that Severely Decrease Microtubule Dynamics Do Not Prevent Nuclear Migration in Yeast

Gupta

Bode

Thrower

et al. 2002

MBoC

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Microtubule dynamics are influenced by interactions of microtubules with cellular factors and by changes in the primary sequence of the tubulin molecule. Mutations of yeast ␤-tubulin C354, which is located near the binding site of some antimitotic compounds, reduce microtubule dynamicity greater than 90% in vivo and in vitro. The resulting intrinsically stable microtubules allowed us to determine which, if any, cellular processes are dependent on dynamic microtubules. The average number of cytoplasmic microtubules decreased from 3 in wild-type to 1 in mutant cells. The single microtubule effectively located the bud site before bud emergence. Although spindles were positioned near the bud neck at the onset of anaphase, the mutant cells were deficient in preanaphase spindle alignment along the mother-bud axis. Spindle microtubule dynamics and spindle elongation rates were also severely depressed in the mutants. The pattern and extent of cytoplasmic microtubule dynamics modulation through the cell cycle may reveal the minimum dynamic properties required to support growth. The ability to alter intrinsic microtubule dynamics and determine the in vivo phenotype of cells expressing the mutant tubulin provides a critical advance in assessing the dynamic requirements of an essential gene function.

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Section: Introductionmentioning

confidence: 99%

β-Tubulin C354 Mutations that Severely Decrease Microtubule Dynamics Do Not Prevent Nuclear Migration in Yeast

Gupta

Bode

Thrower

et al. 2002

MBoC

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“…A long-standing question is how the energy of GTP hydrolysis could be used to generate dynamic instability [6]. Utilizing the outburst of hydrolysis discussed above, we conclude that the energy of GTP hydrolysis may serve to switch the soliton motion in the wall of the microtubule.…”

Section: Simulation Results and Discussionmentioning

confidence: 79%

“…This question has been extensively debated [6,7]. It has been proposed that the force necessary to perform the work of kinetochores could be generated directly by the thermodynamic drive due to microtubule depolymerization [29].…”

Section: Application Of the Modelmentioning

confidence: 99%

“…They consist of intermediate microtubule walls, composed predominantly of less stable, hydrolysed GDP-tubulin subunits, while their ends contain stable GTP-tubulin subunits collectively referred to as the microtubule "GTP-cap". Due to its intrinsic heterogeneity, microtubule growth is endowed with exceptional dynamic features termed "dynamic instability", which refers to the coexistence of both assembly and disassembly phases at the same microtubule end and includes random alternation between these two phases [6]. The question regarding the relationship between hydrolysis of the GTP-cap and dynamic instability has been extensively debated and some consider it as the "holy grail" of the field [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Intrinsic microtubule GTP-cap dynamics in semi-confined systems: kinetochore–microtubule interface

et al. 2012

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In order to quantify the intrinsic dynamics associated with the tip of a GTP-cap under semi-confined conditions, such as those within a neuronal cone and at a kinetochoremicrotubule interface, we propose a novel quantitative concept of critical nano local GTPtubulin concentration (CNLC). A simulation of a rate constant of GTP-tubulin hydrolysis, under varying conditions based on this concept, generates results in the range of 0-420 s −1 . These results are in agreement with published experimental data, validating our model. The major outcome of this model is the prediction of 11 random and distinct outbursts of GTP hydrolysis per single layer of a GTP-cap. GTP hydrolysis is accompanied by an energy release and the formation of discrete expanding zones, built by less-stable, skewed GDP-tubulin subunits. We suggest that the front of these expanding zones within the walls of the microtubule represent soliton-like movements of local deformation triggered by energy released from an outburst of hydrolysis. We propose that these solitons might be helpful in addressing a long-standing question relating to the mechanism underlying how GTP-tubulin hydrolysis controls dynamic instability. This result strongly supports the prediction that large conformational movements in tubulin subunits, termed dynamic transitions, occur as a result of the conversion of chemical energy that is triggered by GTP hydrolysis (Satarić et al., Electromagn Biol Med 24:255-264, 2005). Although simple, the concept of CNLC enables the formulation of a rationale to explain the intrinsic nature of the "push-and-pull" mechanism associated with a kinetochore-microtubule complex. In addition, the capacity of the microtubule wall to produce and mediate localized spatiotemporal excitations, i.e., soliton-like bursts of energy coupled with an abundance of microtubules in dendritic spines supports the hypothesis that microtubule dynamics may underlie neural information processing including neurocomputation (Hameroff,

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“…Rescue, where the microtubule stops depolymerizing and returns to growth, was initially proposed to occur when new GTP-bound tubulin subunits associated with the end of depolymerizing protofilaments, reestablishing the GTP cap (Erickson and O'Brien, 1992). Under this regime, the probability of rescue is related to dimer concentration, because of the microscopic on and off rates of GTP tubulin on the GDP-exposed protofilament ends.…”

Section: Microtubule Polymerization and Dynamic Instabilitymentioning

confidence: 99%