Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons

Janning, Dennis; Igaev, Maxim; Sündermann, Frederik; Brühmann, Jörg; Beutel, Oliver; Heinisch, Jürgen J.; Bakota, Lidia; Piehler, Jacob; Junge, Wolfgang; Brandt, Roland

doi:10.1091/mbc.e14-06-1099

Cited by 144 publications

(145 citation statements)

References 52 publications

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“…Tau and its related family members, MAP2 and MAP4, have repeated microtubule-binding domains that are thought to bind in a series along the microtubule lattice to hold it together and thereby prevent depolymerization (33). However, the on/off rate of these proteins with the microtubule in living cells is only milliseconds (44), which seems inconsistent with tau or its family members stabilizing microtubules in a traditional sense of strong stabilizing protein-protein interactions. Curiously, tau and MAP1b are more enriched on the labile domains of microtubules in the distal region of growing axons than on microtubules in the main shaft of the axon where stable and labile domains intermingle (45-47).…”

Section: Microtubule Dynamics and Stability In Neuronsmentioning

confidence: 99%

Microtubules in health and degenerative disease of the nervous system

Matamoros

Baas

2016

Brain Research Bulletin

113

112

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Microtubules are essential for the development and maintenance of axons and dendrites throughout the life of the neuron, and are vulnerable to degradation and disorganization in a variety of neurodegenerative diseases. Microtubules, polymers of tubulin heterodimers, are intrinsically polar structures with a plus end favored for assembly and disassembly and a minus end less favored for these dynamics. In the axon, microtubules are nearly uniformly oriented with plus ends out, whereas in dendrites, microtubules have mixed orientations. Microtubules in developing neurons typically have a stable domain toward the minus end and a labile domain toward the plus end. This domain structure becomes more complex during neuronal maturation when especially stable patches of polyaminated tubulin become more prominent within the microtubule. Microtubules are the substrates for molecular motor proteins that transport cargoes toward the plus or minus end of the microtubule, with motor-driven forces also responsible for organizing microtubules into their distinctive polarity patterns in axons and dendrites. A vast array of microtubule-regulatory proteins impart direct and indirect changes upon the microtubule arrays of the neuron, and these include microtubule-severing proteins as well as proteins responsible for the stability properties of the microtubules. During neurodegenerative diseases, microtubule mass is commonly diminished, and the potential exists for corruption of the microtubule polarity patterns and microtubule-mediated transport. These ill effects may be a primary causative factor in the disease or may be secondary effects, but regardless, therapeutics capable of correcting these microtubule abnormalities have great potential to improve the status of the degenerating nervous system.

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Section: Microtubule Dynamics and Stability In Neuronsmentioning

confidence: 99%

Microtubules in health and degenerative disease of the nervous system

Matamoros

Baas

2016

Brain Research Bulletin

113

112

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“…In neurons tau shows a highly dynamic interaction with microtubules [25]. The observed "kiss-and-hop" mechanism explains why tau can have multiple additional interaction partners in different cellular compartments.…”

Section: Tau Hyperphosphorylation and Its Relation To Admentioning

confidence: 99%

Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells

Heinisch¹,

Brandt²

2016

MIC

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In the past decade, yeast have been frequently employed to study the molecular mechanisms of human neurodegenerative diseases, generally by means of heterologous expression of genes encoding the relevant hallmark proteins. However, it has become evident that substantial posttranslational modifications of many of these proteins are required for the development and progression of potentially disease relevant changes. This is exemplified by the neuronal tau proteins, which are critically involved in a class of neurodegenerative diseases collectively called tauopathies and which includes Alzheimer's disease (AD) as its most common representative. In the course of the disease, tau changes its phosphorylation state and becomes hyperphosphorylated, gets truncated by proteolytic cleavage, is subject to O-glycosylation, sumoylation, ubiquitinylation, acetylation and some other modifications. This poses the important question, which of these posttranslational modifications are naturally occurring in the yeast model or can be reconstituted by heterologous gene expression. Here, we present an overview on common modifications as they occur in tau during AD, summarize their potential relevance with respect to disease mechanisms and refer to the native yeast enzyme orthologs capable to perform these modifications. We will also discuss potential approaches to humanize yeast in order to create modification patterns resembling the situation in mammalian cells, which could enhance the value of Saccharomyces cerevisiae and Kluyveromyces lactis as disease models.

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“…The mobility of ase1 thus limits its effect on motors. Similarly, the high mobility of individual tau proteins has been put forward to explain why tau expression in cells has no large effect on neuronal transport (Janning et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Streptavidin introduces a pause in motor movement, after which some motors pass the obstacle (Korten and Diez, 2008). More recently is has become clear that many MAPS do not bind firmly to microtubules but instead have a diffusive mode of interaction (Asbury et al, 2006;Kapitein et al, 2008;Janning et al, 2014). So perhaps the roadblock picture, a nonmobile object in the path of the motor protein, is not suited for these proteins.…”

Section: Introductionmentioning

confidence: 99%

Control mechanisms of microtubule overlap regions

Jongerius¹

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Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons

Cited by 144 publications

References 52 publications

Microtubules in health and degenerative disease of the nervous system

Microtubules in health and degenerative disease of the nervous system

Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells

Control mechanisms of microtubule overlap regions

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