Teamwork in microtubule motors

Mallik, Roop; Arpan, K.; Barak, Pradeep; Rai, Ashim; Kunwar, Ambarish

doi:10.1016/j.tcb.2013.06.003

Cited by 86 publications

(103 citation statements)

References 105 publications

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“…It has previously been demonstrated that increasing the number of associated mammalian dynein complexes can stimulate long‐distance movement of beads in vitro (Mallik et al , 2005; Ross et al , 2006). This observation may reflect cooperation between individual heads within different cargo‐associated dynein complexes (Mallik et al , 2013). We therefore considered the possibility that BICD2N and dynactin stimulate processive movement of recombinant human dynein by promoting oligomerisation of the motor complex.…”

Section: Resultsmentioning

confidence: 99%

In vitro reconstitution of a highly processive recombinant human dynein complex

et al. 2014

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Cytoplasmic dynein is an approximately 1.4 MDa multi‐protein complex that transports many cellular cargoes towards the minus ends of microtubules. Several in vitro studies of mammalian dynein have suggested that individual motors are not robustly processive, raising questions about how dynein‐associated cargoes can move over long distances in cells. Here, we report the production of a fully recombinant human dynein complex from a single baculovirus in insect cells. Individual complexes very rarely show directional movement in vitro. However, addition of dynactin together with the N‐terminal region of the cargo adaptor BICD2 (BICD2N) gives rise to unidirectional dynein movement over remarkably long distances. Single‐molecule fluorescence microscopy provides evidence that BICD2N and dynactin stimulate processivity by regulating individual dynein complexes, rather than by promoting oligomerisation of the motor complex. Negative stain electron microscopy reveals the dynein–dynactin–BICD2N complex to be well ordered, with dynactin positioned approximately along the length of the dynein tail. Collectively, our results provide insight into a novel mechanism for coordinating cargo binding with long‐distance motor movement.

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Section: Resultsmentioning

confidence: 99%

In vitro reconstitution of a highly processive recombinant human dynein complex

et al. 2014

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“…In order to include these factors, one may not start from purified motors, but directly work with the whole complexes obtained from cell extracts, as done for example in [33,245] or [156] in semi in vitro experiments.…”

Section: Global View Of Model/experiments Interplaymentioning

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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“…Secondly, one simplification that has been made in our phenomenological model is the assumption of equal load sharing by the motors. However it has been experimentally observed that load is not shared equally between all dynein motors, rather the leading motor of a team of attached motors bears a larger part of the load, which is also demonstrated by bunching of motors at one end [54,85]. Further for dynein motors it has been observed that under load, dynein has a variable step size.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike kinesin, dynein can exhibit catchbonding, where the propensity for the dynein motors to unbind from cellular filament decreases when subjected to increased load force (Fig1b) [29,54,55]. In-vivo experiments on lipid droplets in drosophila embryos have measured the residence times -the time the cargo remains bound before detaching -of cargo driven by kinesin and dynein motors under superstall forces.…”

Section: Introductionmentioning

confidence: 99%

Dynein catch bond as a mediator of codependent bidirectional cellular transport

Puri

Gupta

Chandel

et al. 2018

Preprint

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Intracellular bidirectional transport of cargo on Microtubule filaments is achieved by the collective action of oppositely directed dynein and kinesin motors. Experimental investigations probing the nature of bidirectional transport have found that in certain cases, inhibiting the activity of one type of motor results in an overall decline in the motility of the cellular cargo in both directions.This somewhat counter-intuitive observation, referred to as paradox of codependence is inconsistent with the existing paradigm of a mechanistic tug-of-war between oppositely directed motors.Existing theoretical models do not take into account a key difference in the functionality of kinesin and dynein. Unlike kinesin, dynein motors exhibit catchbonding, wherein the unbinding rates of these motors from the filaments are seen to decrease with increasing force on them. Incorporating this catchbonding behavior of dynein in a theoretical model and using experimentally relevant measures characterizing cargo transport, we show that the functional divergence of the two motors species manifests itself as an internal regulatory mechanism for bidirectional transport and resolves the paradox of codependence. Our model reproduces the key experimental features in appropriate parameter regimes and provides an unifying framework for bidirectional cargo transport. * mithun@phy.iitb.ac.in † sudipto@physics.unipune.ac.in

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Teamwork in microtubule motors

Cited by 86 publications

References 105 publications

In vitro reconstitution of a highly processive recombinant human dynein complex

In vitro reconstitution of a highly processive recombinant human dynein complex

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Dynein catch bond as a mediator of codependent bidirectional cellular transport

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