End-on microtubule-dynein interactions and pulling-based positioning of microtubule organizing centers

Laan, Liedewij; Roth, Sophie; Dogterom, Marileen

doi:10.4161/cc.21753

Cited by 52 publications

(75 citation statements)

References 54 publications

(82 reference statements)

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“…For example, cortical dynein can bind to MT plus-ends and stabilize them, with a length regulation effect, as was confirmed by several in vitro experiments [157,218,217].…”

Section: Motors Action On Mtsmentioning

confidence: 73%

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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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“…For example, cortical dynein can bind to MT plus-ends and stabilize them, with a length regulation effect, as was confirmed by several in vitro experiments [157,218,217].…”

Section: Motors Action On Mtsmentioning

confidence: 73%

“…systems obtained from purified units that are combined to build a specific machinery. In M. Dogterom's group for example, some in vitro experiments have been realized, to study how dyneins attached to an artificial cortex can capture MT plus-ends, stabilize them, and mediate forces [218,217].…”

Section: Global View Of Model/experiments Interplaymentioning

confidence: 99%

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…We use these assays to unravel the nature of MT end interactions with cortical dyneins and to understand centrosome positioning influenced by MT dynamics and dynein pulling at the cortex Laan, Roth, & Dogterom, 2012). The versatility of these reconstituted systems allows for variations in the components in the reaction (molecular motors, MTs-associated proteins, etc.…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

“…Section 4 describes a recent protocol developed in our lab, which involves the use of 3D water-in-oil (w/o) emulsion droplets, in which dyneins are linked to a lipid monolayer at the border of the droplet. This assay is described here for the first time, although some preliminary results were published in a recent review (Laan, Roth, & Dogterom, 2012). Finally, Section 5 explains the advantages and limitations of each assay and discusses interesting additional features that could be added in the future.…”

Section: Introductionmentioning

confidence: 97%

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Reconstitution of Cortical Dynein Function

Roth

Laan

Dogterom

2014

Methods in Enzymology

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Dynein localization and pronuclear movement in the C. elegans zygote

et al. 2022

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Centrosomes serve as a site for microtubule nucleation and these microtubules will grow and interact with the motor protein dynein at the cortex. The position of the centrosomes determines where the mitotic spindle will develop across all cell types. Centrosome positioning is achieved through dynein and microtubule-mediated force generation. The mechanism and regulation of force generation during centrosome positioning are not fully understood. Centrosome and pronuclear movement in the first cell cycle of the Caenorhabditis elegans early embryo undergoes both centration and rotation prior to cell division. The proteins LET-99 and GPB-1 have been postulated to have a role in force generation associated with pronuclear centration and rotation dynamics. When the expression of these proteins is perturbed, pronuclear positioning exhibits a movement defect characterized by oscillatory ("wobble") behavior of the pronuclear complex (PNC). To determine if this movement defect is due to an effect on cortical dynein distribution, we utilize RNAi-mediated knockdown of LET-99 and GPB-1 to induce wobble and assay for any effects on GFP-tagged dynein localization in the early C. elegans embryo. To compare and quantify the movement defect produced by the knockdown of LET-99 and GPB-1, we devised a quantification method that measures the strength of wobble ("wobble metric") observed under these experimental conditions. Our quantification of pronuclear complex dynamics and dynein localization shows that loss of LET-99 and GPB-1 induces a similar movement defect which is independent of cortical dynein localization in the early C. elegans embryo.

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End-on microtubule-dynein interactions and pulling-based positioning of microtubule organizing centers

Cited by 52 publications

References 54 publications

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Reconstitution of Cortical Dynein Function

Dynein localization and pronuclear movement in the C. elegans zygote

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