Kinesin passing permanent blockages along its protofilament track

Dreblow, Kerstin; Kalchishkova, Nikolina; Böhm, Konrad J.

doi:10.1016/j.bbrc.2010.04.035

Cited by 17 publications

(23 citation statements)

References 30 publications

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“…The width of side steps seems compatible with the single kinesin heads steps [100,394]. Side-stepping still remains a rare event for kinesin-1, while some representatives of the kinesin-2 class were found in vivo to perform left-handed spiraling around microtubules [61].…”

Section: Experimental Observationsmentioning

confidence: 62%

“…The authors suggest as the most probable interpretation of this fact that kinesin can change protofilament, though another explanation could be that kinesins detach and reattach shortly after, while being kept weekly bound with the obstacle. Some experiments reported by Dreblow et al [100] confirm 55 Figure 35: Particle-particle interactions in a two-species TASEP, as studied in [197]. The attachment (detachment) rate increases (decreases) by a factor q if the next site is occupied by a particle of the same species.…”

Section: Experimental Observationsmentioning

confidence: 67%

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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: Experimental Observationsmentioning

confidence: 62%

Section: Experimental Observationsmentioning

confidence: 67%

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…For axonemal dynein motors, off-axis movement-causing microtubule rotations and, thus, torque-may be important for the three-dimensional motion of the flagellar beat (12,13); for cytoplasmic dynein, sideward steps may be an essential biological requirement such that heads can pass each other, obstacles, or counter-propagating kinesin motors (15)(16)(17)40). For kinesin motors, the ability to bypass obstacles is also an essential property for cargo transport (41)(42)(43). How torque generation (12,13,(18)(19)(20)(21) on the cargo, i.e., a rotation of the cargo around the filament axis, induced by sideward stepping influences cargo transport remains to be seen.…”

Section: Discussionmentioning

confidence: 99%

The Kinesin-8 Kip3 Switches Protofilaments in a Sideward Random Walk Asymmetrically Biased by Force

Bugiel

Böhl

Schäffer

2015

Biophysical Journal

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Molecular motors translocate along cytoskeletal filaments, as in the case of kinesin motors on microtubules. Although conventional kinesin-1 tracks a single microtubule protofilament, other kinesins, akin to dyneins, switch protofilaments. However, the molecular trajectory-whether protofilament switching occurs in a directed or stochastic manner-is unclear. Here, we used high-resolution optical tweezers to track the path of single budding yeast kinesin-8, Kip3, motor proteins. Under applied sideward loads, we found that individual motors stepped sideward in both directions, with and against loads, with a broad distribution in measured step sizes. Interestingly, the force response depended on the direction. Based on a statistical analysis and simulations accounting for the geometry, we propose a diffusive sideward stepping motion of Kip3 on the microtubule lattice, asymmetrically biased by force. This finding is consistent with previous multimotor gliding assays and sheds light on the molecular switching mechanism. For kinesin-8, the diffusive switching mechanism may enable the motor to bypass obstacles and reach the microtubule end for length regulation. For other motors, such a mechanism may have implications for torque generation around the filament axis.

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“…(d) A more realistic motor and cargo size will influence the ability of lane changes to overcome blockages. Finally (e) static obstructions such as MAPs (microtubule associated proteins) will influence the behaviour of motors on the MT by increasing more potential blockages [24,31,32,33]; a high concentration of these will clearly influence the transport efficiency. At present, quantitative data for most of these processes are not available for any living cell.…”

Section: Discussionmentioning

confidence: 99%

“…The lane-change rules in the latter model are based on experimental observations that (a) dynein can switch between lanes on the MT at a certain rate [22], whereas (b) kinesin remains on a single lane [23], and (c) no long-lasting traffic jam is observed between particles away from the tip. However, recent reports show that kinesin can change lanes to overcome obstacles on the MT [24]. Thus the situation in the living cell is less clear and one aim of this paper is to investigate the impact of different lane-change rules on bidirectional transport.…”

Section: Introductionmentioning

confidence: 99%

Bidirectional transport and pulsing states in a multi-lane ASEP model

Lin¹,

Steinberg²,

Ashwin³

2011

J. Stat. Mech.

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Abstract. In this paper, we introduce an ASEP-like transport model for bidirectional motion of particles on a multi-lane lattice. The model is motivated by in vivo experiments on organelle motility along a microtubule (MT), consisting of thirteen protofilaments, where particles are propelled by molecular motors (dynein and kinesin). In the model, organelles (particles) can switch directions of motion due to "tug-of-war" events between counteracting motors. Collisions of particles on the same lane can be cleared by switching to adjacent protofilaments (lane changes).We analyze transport properties of the model with no-flux boundary conditions at one end of a MT ("plus-end" or tip). We show that the ability of lane changes can affect the transport efficiency and the particle-direction change rate obtained from experiments is close to optimal in order to achieve efficient motor and organelle transport in a living cell. In particular, we find a nonlinear scaling of the mean tip size (the number of particles accumulated at the tip) with injection rate and an associated phase transition leading to pulsing states characterized by periodic filling and emptying of the system.

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Kinesin passing permanent blockages along its protofilament track

Cited by 17 publications

References 30 publications

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

The Kinesin-8 Kip3 Switches Protofilaments in a Sideward Random Walk Asymmetrically Biased by Force

Bidirectional transport and pulsing states in a multi-lane ASEP model

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