Crowding of Molecular Motors Determines Microtubule Depolymerization

Reese, Louis; Melbinger, Anna; Frey, Erwin

doi:10.1016/j.bpj.2011.11.239

Cited by 19 publications

(32 citation statements)

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“…Exclusion processes have been used to model the collective behavior of such depolymerases [303]. The model predicts some collective effects through the jamming of polymerases, that would affect the depolymerization speed.…”

Section: Motors Action On Mtsmentioning

confidence: 99%

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: Motors Action On Mtsmentioning

confidence: 99%

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…Longer microtubules recruit more kinesin motors from the cytoplasm, which results in a length-dependent rate of disassembly. When this is combined with a length-independent rate of assembly, a unique steady-state microtubule length is obtained (12)(13)(14)(15)(16)(17). A related mechanism involves the modulation of microtubular dynamic instabilities, that is, the catastrophe frequency (18,19).…”

Section: Introductionmentioning

confidence: 99%

Delayed Feedback Model of Axonal Length Sensing

Karamched

Bressloff

2015

Biophysical Journal

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A fundamental question in cell biology is how the sizes of cells and organelles are regulated at various stages of development. Size homeostasis is particularly challenging for neurons, whose axons can extend from hundreds of microns to meters (in humans). Recently, a molecular-motor-based mechanism for axonal length sensing has been proposed, in which axonal length is encoded by the frequency of an oscillating retrograde signal. In this article, we develop a mathematical model of this length-sensing mechanism in which advection-diffusion equations for bidirectional motor transport are coupled to a chemical signaling network. We show that chemical oscillations emerge due to delayed negative feedback via a Hopf bifurcation, resulting in a frequency that is a monotonically decreasing function of axonal length. Knockdown of either kinesin or dynein causes an increase in the oscillation frequency, suggesting that the length-sensing mechanism would produce longer axons, which is consistent with experimental findings. One major prediction of the model is that fluctuations in the transport of molecular motors lead to a reduction in the reliability of the frequency-encoding mechanism for long axons.

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“…Do similar principles operate at the molecular level? Traffic jams of motor proteins on cytoskeletal filaments have been predicted theoretically (12)(13)(14)(15)(16), and experiments with purified proteins indicate that motor proteins have properties that may predispose them to form traffic jams: In principle, almost all the motor-binding sites on a microtubule can be occupied if the kinesin-1 (17,18), kinesin-3 (15), or kinesin-8 (19) concentration is high enough. Moreover, abrupt local increases in kinesin-1 density on a microtubule have been reported (15), but whether these were associated with an abrupt decrease in speed was not investigated in these experiments.…”

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confidence: 99%

Molecular crowding creates traffic jams of kinesin motors on microtubules

Leduc

Padberg‐Gehle

Varga

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

201

242

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Despite the crowdedness of the interior of cells, microtubule-based motor proteins are able to deliver cargoes rapidly and reliably throughout the cytoplasm. We hypothesize that motor proteins may be adapted to operate in crowded environments by having molecular properties that prevent them from forming traffic jams. To test this hypothesis, we reconstituted high-density traffic of purified kinesin-8 motor protein, a highly processive motor with long end-residency time, along microtubules in a total internal-reflection fluorescence microscopy assay. We found that traffic jams, characterized by an abrupt increase in the density of motors with an associated abrupt decrease in motor speed, form even in the absence of other obstructing proteins. To determine the molecular properties that lead to jamming, we altered the concentration of motors, their processivity, and their rate of dissociation from microtubule ends. Traffic jams occurred when the motor density exceeded a critical value (density-induced jams) or when motor dissociation from the microtubule ends was so slow that it resulted in a pileup (bottleneck-induced jams). Through comparison of our experimental results with theoretical models and stochastic simulations, we characterized in detail under which conditions densityand bottleneck-induced traffic jams form or do not form. Our results indicate that transport kinesins, such as kinesin-1, may be evolutionarily adapted to avoid the formation of traffic jams by moving only with moderate processivity and dissociating rapidly from microtubule ends.

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Crowding of Molecular Motors Determines Microtubule Depolymerization

Cited by 19 publications

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Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Delayed Feedback Model of Axonal Length Sensing

Molecular crowding creates traffic jams of kinesin motors on microtubules

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