Single-molecule investigation of the interference between kinesin, tau and MAP2c

Seitz, Arne; Kojima, Hiroaki; Oiwa, Kazuhiro; Mandelkow, Eva‐Maria; Song, Young Ho

doi:10.1093/emboj/cdf503

Cited by 228 publications

(251 citation statements)

References 48 publications

(70 reference statements)

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“…The interaction of dyneins with tau proteins are similar to those reported for kinesin: Run lengths are decreased at high concentrations of tau on the MT [336]. In contrast to kinesin, dynein does not detach at encounters of tau but tends to reverse direction, maybe by switching to the diffusive state of motion described above [97].…”

Section: Modification Of Mts By Maps : the Example Of Tau Proteinssupporting

confidence: 70%

“…In fact, it has been shown in vitro that kinesin's attachment to the MT is hindered by tau, whereas kinesin is not affected in its motion along the filament once it is bound, i.e., processivity and walking speeds are unaffected [336,365,396]. On the other hand, another study found that kinesin had a higher probability of detachment when encountering tau patches on the MT [97].…”

Section: Modification Of Mts By Maps : the Example Of Tau Proteinsmentioning

confidence: 99%

“…As already mentioned, MT-bound tau interferes with the attachment of both motor families, kinesin and dynein, but the effect is more pronounced for kinesin [365,336]. At normal tau concentrations, this may allow tau to regulate the directionality of axonal transport [97].…”

Section: Structural Defects Of the Mt Networkmentioning

confidence: 99%

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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: Modification Of Mts By Maps : the Example Of Tau Proteinssupporting

confidence: 70%

Section: Modification Of Mts By Maps : the Example Of Tau Proteinsmentioning

confidence: 99%

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Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…207,213,214 Four-repeat tau binds microtubules with a higher affinity than three-repeat tau, and an isoform imbalance in favor of four-repeat isoforms might impair kinesin-dependent anterograde traffic, because tau and kinesins bind to the microtubule surface in a competitive fashion. 28,30,146 Shifting the tau isoform ratio from fourrepeat to three-repeat isoforms by alternative splicing was therefore proposed as a therapeutic option in tauopathies. Promising results have already been achieved, with antisense oligonucleotides directed against the splice junction of exon 10 in PC12 cells leading to reduced exon 10 splicing.…”

Section: Isoform Approachesmentioning

confidence: 99%

Tau-Based Treatment Strategies in Neurodegenerative Diseases

2008

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Summary:Neurofibrillary tangles are a characteristic hallmark of Alzheimer's and other neurodegenerative diseases, such as Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). These diseases are summarized as tauopathies, because neurofibrillary tangles are composed of intracellular aggregates of the microtubule-associated protein tau. The molecular mechanisms of tau-mediated neurotoxicity are not well understood; however, pathologic hyperphosphorylation and aggregation of tau play a central role in neurodegeneration and neuronal dysfunction. The present review, therefore, focuses on therapeutic approaches that aim to inhibit tau phosphorylation and aggregation or to dissolve preexisting tau aggregates. Further experimental therapy strategies include the enhancement of tau clearance by activation of proteolytic, proteasomal, or autophagosomal degradation pathways or anti-tau directed immunotherapy. Hyperphosphorylated tau does not bind microtubules, leading to microtubule instability and transport impairment. Pharmacological stabilization of microtubule networks might counteract this effect. In several tauopathies there is a shift toward four-repeat tau isoforms, and interference with the splicing machinery to decrease four-repeat splicing might be another therapeutic option.

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“…Another possible role for tau is the regulation of kinesin-based transport (Ebneth et al 1998;Sparacino et al 2014;Terwel et al 2002). Tau reduces the attachment of kinesins to MTs and interferes with their transport when is overexpressed, in both in vivo and in vitro experiments (Dixit et al 2008;Ebneth et al 1998;Seitz et al 2002;Stamer et al 2002;Trinczek et al 1999;Vershinin et al 2007).…”

Section: Tau/mapt Family Of Microtubule-associated Proteinsmentioning

confidence: 99%

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

2016

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Dendrites have a unique microtubule organization. In vertebrates, dendritic microtubules are organized in antiparallel bundles, oriented with their plus ends either pointing away or toward the soma. The mixed microtubule arrays control intracellular trafficking and local signaling pathways, and are essential for dendrite development and function. The organization of microtubule arrays largely depends on the combined function of different microtubule regulatory factors or generally named microtubule-associated proteins (MAPs). Classical MAPs, also called structural MAPs, were identified more than 20 years ago based on their ability to bind to and copurify with microtubules. Most classical MAPs bind along the microtubule lattice and regulate microtubule polymerization, bundling, and stabilization. Recent evidences suggest that classical MAPs also guide motor protein transport, interact with the actin cytoskeleton, and act in various neuronal signaling networks. Here, we give an overview of microtubule organization in dendrites and the role of classical MAPs in dendrite development, dendritic spine formation, and synaptic plasticity. IntroductionMicrotubules (MTs) are cytoskeletal structures that play essential roles in all eukaryotic cells. MTs are important not only during cell division but also in non-dividing cells, where they are critical structures in numerous cellular processes such as cell motility, migration, differentiation, intracellular transport and organelle positioning. MTs are composed of two proteins, α-and β-tubulin, that form heterodimers and organize themselves in a head-to-tail manner. MTs are dynamic and they can rapidly switch between cycles of growth and shrinkage. This MT

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Single-molecule investigation of the interference between kinesin, tau and MAP2c

Cited by 228 publications

References 48 publications

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Tau-Based Treatment Strategies in Neurodegenerative Diseases

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

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