A theory of microtubule catastrophes and their regulation

Brun, Ludovic; Rupp, Beat; Ward, Jonathan J.; Nédélec, François

doi:10.1073/pnas.0910774106

Cited by 79 publications

(112 citation statements)

References 35 publications

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“…Nevertheless, these models exhibit a macroscopically observable behavior which reproduces the long periods of persistent growth and shrinkage characteristic for the dynamic instability of MTs [126,247,12,60]. The rescue and catastrophe rates assumed in section 2.3 are in these models observables which result from the kinetics of the tubulin subunits with GDP or GTP.…”

Section: Models With Explicit Description Of the Gtp Capmentioning

confidence: 99%

“…Therefore, a different class of MT models has been suggested, which does not postulate switching between a growing and a shrinking state, but describes the process at a more refined scale [126,247,12,60]. In these models, individual tubulin subunits are allowed at all times to be added to or removed from the plus-end.…”

Section: Models With Explicit Description Of the Gtp Capmentioning

confidence: 99%

“…Structural changes at the tip, interactions between protofilaments, or MAPs, could also play a role [60]. Comparing models and experiments in various situations could help to distinguish between these different scenarios, as we will illustrate below by the example of dynamic MTs in finite volume.…”

Section: Models With Explicit Description Of the Gtp Capmentioning

confidence: 99%

“…On the other hand, another study found that kinesin had a higher probability of detachment when encountering tau patches on the MT [97]. 60 As a consequence of the fact that tau proteins may prevent locally kinesins to bind, tau proteins have been also shown to favor switches of cargos from one microtubule to another one [310], a feature which may be helpful in crowded environments.…”

Section: Modification Of Mts By Maps : the Example Of Tau Proteinsmentioning

confidence: 99%

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Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized.The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach.It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer.We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal transport, because of its relevance for neuronal diseases. Some important characteristics of axonal transport is that it takes place in a confined environment; Besides several types of motors are involved, that move in opposite directions. It is a challenge to understand how this bidirectional transport is organized. We review several features that could contribute to the efficiency of bidirectional transport in the axon, including in particular the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we also discuss some open questions that may be relevant for future research in this field.

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Section: Models With Explicit Description Of the Gtp Capmentioning

confidence: 99%

Section: Models With Explicit Description Of the Gtp Capmentioning

confidence: 99%

Section: Models With Explicit Description Of the Gtp Capmentioning

confidence: 99%

Section: Modification Of Mts By Maps : the Example Of Tau Proteinsmentioning

confidence: 99%

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Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…A large variety of approaches have been adopted to tackle the problem of microtubule dynamics based on the GTP cap theory [6][7][8][9][10][11][12][13][14][15], which differ essentially in the level of molecular details included in the respective models. As recently discussed by Margolin et al [15], the results from all models, by parameter tuning, appear to agree with available experimental observations irrespective of the details of microtubule structure included, and irrespective of the differences in mathematical expressions for (primarily) the frequency of catastrophe or related quantities.…”

Section: Introductionmentioning

confidence: 99%

Microtubule catastrophe from protofilament dynamics

Jemseena¹,

Gopalakrishnan²

2013

Phys. Rev. E

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The disappearance of the guanosine triphosphate (GTP)-tubulin cap is widely believed to be the forerunner event for the growth-shrinkage transition ('catastrophe') in microtubule filaments in eukaryotic cells. We study a discrete version of a stochastic model of the GTP cap dynamics, originally proposed by Flyvbjerg, Holy andLeibler (Flyvbjerg, Holy and Leibler, Phys. Rev. Lett. 73, 2372, 1994). Our model includes both spontaneous and vectorial hydrolysis, as well as dissociation of a non-hydrolyzed dimer from the filament after incorporation. In the first part of the paper, we apply this model to a single protofilament of a microtubule. A catastrophe transition is defined for each protofilament, similar to the earlier one-dimensional models, the frequency of occurrence of which is then calculated under various conditions, but without explicit assumption of steady state conditions. Using a perturbative approach, we show that the leading asymptotic behavior of the prot ofilament catastrophe in the limit of large growth velocities is remarkably similar across different models. In the second part of the paper, we extend our analysis to the entire filament by making a conjecture that a minimum number of such transitions are required to occur for the onset of microtubule catastrophe. The frequency of microtubule catastrophe is then determined using numerical simulations, and compared with analytical/semi-analytical estimates made under steady state/quasi-steady state assumptions respectively for the protofilament dynamics. A few relevant experimental results are analyzed in detail, and compared with predictions from the model. Our results indicate that loss of GTP cap in 2-3 protofilaments is necessary to trigger catastrophe in a microtubule.

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

et al. 2013

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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.

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A theory of microtubule catastrophes and their regulation

Cited by 79 publications

References 35 publications

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Microtubule catastrophe from protofilament dynamics

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

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