Two Kinesins Transport Cargo Primarily via the Action of One Motor: Implications for Intracellular Transport

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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“…Typically, a coated bead is attached to the motor [357,166]. The bead is placed in an optical trap, while the motor steps on a MT (Fig.…”

Section: Kinesin and Dynein Under Loadmentioning

confidence: 99%

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…In principle they can be determined experimentally by careful analysis of trajectories of two-motor complexes provided that the cargo states C 1 and C 2 can be identified. This approach has been taken in a series of recent studies by Diehl and collaborators, 34,48,53 who distinguish microstates with one or two load-bearing motors, although these do not necessarily correspond to the states C 1 and C 2 with one or two bound motors, if the motors do not share the load. 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.…”

Section: General Theoretical Frameworkmentioning

confidence: 99%

“…23 However, a recent study suggested that the load may not always be shared equally by the motors. 34 Finally, transport by multiple motors provides additional opportunities for the regulation of transport as illustrated by the effects of microtubule-associated proteins. 60,18 In recent years, it has therefore become more and more evident that to understand transport processes in cells, one has to move beyond single motors and study the cooperative action of several motors or motor assemblies and the mechanism by which these motors are coordinated.…”

Section: Introductionmentioning

confidence: 99%

“…An important improvement for studying motor cooperation was thus the design of synthetic assemblies of precisely defined numbers of motors. 48,53,63 Since then a number of studies have investigated such defined motor complexes: The most extensive studies have been done for a system of two kinesin-1 motors coupled via a DNA scaffold, 34,53 but other studies have also used two kinesins coupled via an antibody, 63 two coupled myosin V motors, 48 and a myosin V motor coupled to a myosin VI motor. 1 Motor cooperation has also been studied with microtubule gliding assays, in which motors immobilized on a surface pull a microtubule along that surface.…”

Section: Introductionmentioning

confidence: 99%

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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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Two Kinesins Transport Cargo Primarily via the Action of One Motor: Implications for Intracellular Transport

Cited by 126 publications

References 34 publications

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

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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