Tau Protein Diffuses along the Microtubule Lattice

Hinrichs, Maike H.; Jalal, Avesta; Brenner, Bernhard; Mandelkow, Eckhard; Kumar, Satish; Scholz, Tim

doi:10.1074/jbc.m112.369785

Cited by 133 publications

(169 citation statements)

References 55 publications

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“…4C) and previous work demonstrating that TPX2 does not inhibit kinesin-1 in a gliding assay (11). In contrast, Tau, which binds along the outer ridge and requires the E-hook for lattice diffusion (35), induces the release of kinesin motors, including both kinesin-1 and Eg5, from the microtubule. This suggests that the location of MAP binding to the microtubule lattice results in differential effects on motor behavior (e.g.…”

Section: Tpx2 Differentially Inhibits Microtubule Gliding By Eg5mentioning

confidence: 99%

“…Somewhat surprisingly, our results show that the C-terminal tails of tubulin, the E-hooks, do not contribute to TPX2 interaction with the microtubule. Other MAPs, including Tau, She1, and XMAP215, require the tubulin E-hooks for microtubule binding (15,34,35). Additionally, the processivity of kinesin-1 and dynein motors and the diffusive end targeting of MCAK are enhanced by the E-hooks (36 -38).…”

Section: Tpx2 Differentially Inhibits Microtubule Gliding By Eg5mentioning

confidence: 99%

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TPX2 Inhibits Eg5 by Interactions with Both Motor and Microtubule

Balchand

Mann

Titus

et al. 2015

Journal of Biological Chemistry

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Background: TPX2 is a mitotic microtubule-associated protein that regulates the kinesin, Eg5. Results: Full-length TPX2 is a more potent inhibitor of Eg5 velocity than truncated TPX2; differential regulation by TPX2 was not observed for monomeric Eg5. Conclusion: TPX2 inhibits Eg5 as a roadblock and by direct interaction with Eg5. Significance: TPX2 may contribute to the spatial and temporal regulation of the mitotic motor Eg5.

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Section: Tpx2 Differentially Inhibits Microtubule Gliding By Eg5mentioning

confidence: 99%

Section: Tpx2 Differentially Inhibits Microtubule Gliding By Eg5mentioning

confidence: 99%

TPX2 Inhibits Eg5 by Interactions with Both Motor and Microtubule

Balchand

Mann

Titus

et al. 2015

Journal of Biological Chemistry

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show abstract

“…Tau must first detach from MTs before it can diffuse in the cytoplasm. There are also reports suggesting that some of the MT-bound tau can diffuse along MTs [25].…”

Section: Introductionmentioning

confidence: 99%

Simulating tubulin-associated unit transport in an axon: using bootstrapping for estimating confidence intervals of best-fit parameter values obtained from indirect experimental data

Кузнецов

2017

Proc. R. Soc. A.

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In this paper, we first develop a model of axonal transport of tubulin-associated unit (tau) protein. We determine the minimum number of parameters necessary to reproduce published experimental results, reducing the number of parameters from 18 in the full model to eight in the simplified model. We then address the following questions: Is it possible to estimate parameter values for this model using the very limited amount of published experimental data? Furthermore, is it possible to estimate confidence intervals for the determined parameters? The idea that is explored in this paper is based on using bootstrapping. Model parameters were estimated by minimizing the objective function that simulates the discrepancy between the model predictions and experimental data. Residuals were then identified by calculating the differences between the experimental data and model predictions. New, surrogate ‘experimental’ data were generated by randomly resampling residuals. By finding sets of best-fit parameters for a large number of surrogate data the histograms for the model parameters were produced. These histograms were then used to estimate confidence intervals for the model parameters, by using the percentile bootstrap. Once the model was calibrated, we applied it to analysing some features of tau transport that are not accessible to current experimental techniques.

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“…The latter induce microglia and astrocyte activation, and are typically surrounded by dystrophic, tau-containing neurites. Hyperphosporylated tau protein is the main component of NFTs, which are located in the cytoplasm of neuronal cell bodies and neuritic processes (Buee et al 2000;Hinrichs et al 2012;Simic et al 1998). …”

Section: Introductionmentioning

confidence: 99%

Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer’s disease

et al. 2015

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Immunohistochemistry and electron microscopy analysis were used to detect amyloid β-(Aβ 1-42 ) and hyperphosphorylated tau (AT8) accumulation and ultrastructural changes in the brain. Memory decline was time-(≤3 months/acute, ≥3 months/progressive) and STZ-icv dosedependent. Morphological changes were manifested as thinning of parietal cortex (≥1 month) and corpus callosum (9 months), and were more pronounced in the 3 mg/kg STZ group. Early neurofibrillary changes (AT8) were detected from 1 month onward in the neocortex, and progressed after 3 months to the hippocampus. Intracellular Aβ 1-42 accumulation was found in the neocortex at 3 months following STZ-icv treatment, while diffuse Aβ 1-42 -positive plaque-like formations were found after 6 months in the neocortex and hippocampus. Ultrastructural changes revealed enlargement of Golgi apparatus, pyknotic nuclei, and timedependent increase in lysosome size, number, and density. Our data provide a staging of cognitive, structural/ultrastructural, and neuropathological markers in the STZ-icv rat model that in many aspects seems to be generally comparable to stages seen in human sAD.

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Tau Protein Diffuses along the Microtubule Lattice

Cited by 133 publications

References 55 publications

TPX2 Inhibits Eg5 by Interactions with Both Motor and Microtubule

TPX2 Inhibits Eg5 by Interactions with Both Motor and Microtubule

Simulating tubulin-associated unit transport in an axon: using bootstrapping for estimating confidence intervals of best-fit parameter values obtained from indirect experimental data

Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer’s disease

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