Tau Protects Microtubules in the Axon from Severing by Katanin

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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“…It was also hypothesized that tau has a protective function for MTs against the action of the MT-severing protein katanin [298].…”

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

confidence: 99%

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…39 The activity of microtubule-severing enzymes is not restricted to dendrites; they are also required for axonal growth. 40,42,43 Spatial regulation of microtubule-severing enzyme activity in neurons is controlled by mechanisms such as the binding of the microtubule-associated protein Tau to microtubules in hippocampal neuron axons 44 and the post-translational modification of dendrite microtubules (polyglutamylation). 45 g-tubulin and microtubule-severing pathways interact in nonneuronal cells, for example to organize meiotic spindle microtubules in C. elegans.…”

Section: Microtubule Seeds In Dendritesmentioning

confidence: 99%

Microtubule nucleation and organization in dendrites

2016

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“…It is possible that some microtubuleassociated proteins (MAP) may preferentially bind to the microtubules in dendrites or those in axons and thus provide differential protection against the microtubule-severing activity of Kat-60L1. For example, in cultured rat hippocampal neurons, the microtubules in dendrites are more susceptible to excess activity of overexpressed Katanin p60 than those in axons (30), and the axonal Tau proteins protect axonal microtubules from severing by Katanin (31). The differential binding preference for microtubules in dendrites versus axons could also arise from regional posttranslational modification of MAPs.…”

Section: The Restriction Of Severing Activity In Dendrites But Not Inmentioning

confidence: 99%

Drosophila IKK-related kinase Ik2 and Katanin p60-like 1 regulate dendrite pruning of sensory neuron during metamorphosis

Lee

Jan

2009

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

118

149

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Pruning is a widely observed mechanism for developing nervous systems to refine their circuitry. During metamorphosis, certain Drosophila sensory neurons undergo large-scale dendrite pruning to remove their larval branches before regeneration of their adult dendrites. Dendrite pruning involves dendrite severing, followed with debris removal. Little is known about the molecular mechanisms underlying dendrite severing. Here, we show that both the Ik2 kinase and Katanin p60-like 1 (Kat-60L1) of the Katanin family of microtubule severing proteins are required for dendrite severing. Mutant neurons with disrupted Ik2 function have diminished ability in severing their larval dendrites in pupae. Conversely, premature activation of Ik2 triggers precocious dendrite severing in larvae, revealing a critical role of Ik2 in initiating dendrite severing. We found a role for Kat-60L1 in facilitating dendrite severing by breaking microtubule in proximal dendrites, where the dendrites subsequently separate from the soma. Our study thus implicates Ik2 and Kat-60L1 in dendrite severing that involves local microtubule disassembly.Ik2/IKK ͉ microtubule severing

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Tau Protects Microtubules in the Axon from Severing by Katanin

Cited by 214 publications

References 53 publications

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Microtubule nucleation and organization in dendrites

Drosophila IKK-related kinase Ik2 and Katanin p60-like 1 regulate dendrite pruning of sensory neuron during metamorphosis

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