Detection of fractional steps in cargo movement by the collective operation of kinesin-1 motors

Leduc, Cécile; Ruhnow, Felix; Howard, Jonathon; Diez, Stefan

doi:10.1073/pnas.0701864104

Cited by 131 publications

(138 citation statements)

References 42 publications

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“…As shown in previous experimental (7,21) and theoretical studies (8,9,11,22), the more motors that are attached to a cargo, the farther the cargo can travel along the microtubule. Particularly, for relatively small cargo such as a Qdot, forces due to fluctuations dominate, and motor dissociation from the track is a Poissonian process.…”

Section: Discussionmentioning

confidence: 97%

Motor transport of self-assembled cargos in crowded environments

Conway¹,

Wood

Tüzel

et al. 2012

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

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Intracellular transport of cargo particles is performed by multiple motors working in concert. However, the mechanism of motor association to cargos is unknown. It is also unknown how long individual motors stay attached, how many are active, and how multimotor cargos would navigate a densely crowded filament with many other motors. Prior theoretical and experimental biophysical model systems of intracellular cargo have assumed fixed teams of motors transporting along bare microtubules or microtubules with fixed obstacles. Here, we investigate a regime of cargos transporting along microtubules crowded with free motors. Furthermore, we use cargos that are able to associate or dissociate motors as it translocates. We perform in vitro motility reconstitution experiments with high-resolution particle tracking. Our model system consists of a quantum dot cargo attached to kinesin motors, and additional free kinesin motors that act as traffic along the microtubule. Although high densities of kinesin motors hinder forward motion, resulting in a lower velocity, the ability to associate motors appears to enhance the run length and attachment time of the quantum dot, improving overall cargo transport. These results suggest that cargos that can associate new motors as they transport could overcome traffic jams.axonal transport | cytoplasmic dynein

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Section: Discussionmentioning

confidence: 97%

Motor transport of self-assembled cargos in crowded environments

Conway¹,

Wood

Tüzel

et al. 2012

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

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“…Likewise, in gliding assays, trajectories can be partitioned into segments with one or two motor pulling the microtubule based on the different swiveling behavior of the microtubule. 45 FIGURE 1. Theoretical description of two coupled molecular motors.…”

Section: General Theoretical Frameworkmentioning

confidence: 99%

“…1 Motor cooperation has also been studied with microtubule gliding assays, in which motors immobilized on a surface pull a microtubule along that surface. 8,45 In parallel to these experimental efforts, the dynamics of teams of cytoskeletal motors has also been tackled by theoretical and computational approaches. A general theoretical framework for studying motor teams has been proposed in 2005 by our group.…”

Section: Introductionmentioning

confidence: 99%

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

et al. 2012

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Abstract-Engineered constructs coupling a defined number of molecular motors provide an opportunity to study the cooperative transport of cargoes. Theoretical descriptions for the dynamics of such complexes can help to understand experimental data or to quantitatively formulate expectations for such experiments and provide a general framework for such analysis. Here, we review and extend recent theoretical studies that focused on pairs of molecular motors to study effects of coupling between the motors. We derive explicit results for two elastically coupled kinesin-1 motors as a function of the coupling strength using both linear and nonlinear springs. In addition, we discuss the general dynamics of such motor pairs, which is governed by characteristic time scales for the spontaneous unbinding of motors and for the built-up of strain forces that are sufficiently large to affect the run length and/or the velocity of the motors. We show how the comparison of these time scales can be used to predict the distinct behavior of different motor species, the effects of coupling, and the impact of the single motor velocity on the observable dynamics of a motor pair.

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“…Therefore, investigators have designed in vitro experiments to limit the number of coupled motors so that mechanistic modeling efforts were tractable (8)(9)(10)(11). For these models, the velocity and direction of cargo transport generated by ensembles of antagonistic motors depended solely on the relative number of motors pulling in either direction (12,13).…”

mentioning

confidence: 99%

Myosin Va and myosin VI coordinate their steps while engaged in an in vitro tug of war during cargo transport

Safer³

et al. 2011

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

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Myosin Va (myoV) and myosin VI (myoVI) are processive molecular motors that transport cargo in opposite directions on actin tracks. Because these motors may bind to the same cargo in vivo, we developed an in vitro "tug of war" to characterize the stepping dynamics of single quantum-dot-labeled myoV and myoVI motors linked to a common cargo. MyoV dominates its myoVI partner 79% of the time. Regardless of which motor wins, its stepping rate slows due to the resistive load of the losing motor (myoV, 2.1 pN; myoVI, 1.4 pN). Interestingly, the losing motor steps backward in synchrony with the winning motor. With ADP present, myoVI acts as an anchor to prevent myoV from stepping forward. This model system emphasizes the physical communication between opposing motors bound to a common cargo and highlights the potential for modulating this interaction by changes in the cell's ionic milieu.intracellular transport | motility assay | processivity | single molecule biophysics I ntracellular cargo transport relies on at least two classes of myosin molecular motors to navigate the actin cytoskeleton. Class V (myoV) and class VI (myoVI) myosins are double-headed motors that transport cargo in opposite directions along polarized actin filament tracks (1, 2). These motors convert the energy of ATP hydrolysis into force and motion and in doing so step processively on actin in a hand-over-hand fashion. With the plusends of actin filaments oriented toward the cell periphery, myoV transport contributes to exocytosis, whereas myoVI transport is critical to endocytosis (1, 2). Ensembles of molecular motors share the responsibility for transporting a single vesicle. For example, approximately 60 myoV motors coat a melanosome, although a smaller number is likely to be engaged with the track at any given time (3). Transport can also be bidirectional when oppositely directed motors are operative, as for axonal transport by the microtubule-based motors, kinesin and dynein (4, 5). With myoV and myoVI colocalizing to organelles (6, 7), these motors may engage in a virtual tug of war. If so, how do these oppositely directed myosin motors mechanically interact so that cargo is efficiently delivered to its destination?Individual motors within a transport ensemble may coordinate, cooperate, or mechanically impede one another, but determining by which mode they operate is complicated by the cargo geometry, the number and directionality of engaged motors, and the physical challenges presented by the dense actin cytoskeleton. Therefore, investigators have designed in vitro experiments to limit the number of coupled motors so that mechanistic modeling efforts were tractable (8-11). For these models, the velocity and direction of cargo transport generated by ensembles of antagonistic motors depended solely on the relative number of motors pulling in either direction (12, 13). The mechanical interactions between motors and the resultant stepping dynamics of each motor within the ensemble were beyond the predictive capacity of these models. Therefore, ...

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Detection of fractional steps in cargo movement by the collective operation of kinesin-1 motors

Cited by 131 publications

References 42 publications

Motor transport of self-assembled cargos in crowded environments

Motor transport of self-assembled cargos in crowded environments

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

Myosin Va and myosin VI coordinate their steps while engaged in an in vitro tug of war during cargo transport

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