author_facet Weissmann, Carina
Reyher, Hans‐Jürgen
Gauthier, Anne
Steinhoff, Heinz‐Jürgen
Junge, Wolfgang
Brandt, Roland
Weissmann, Carina
Reyher, Hans‐Jürgen
Gauthier, Anne
Steinhoff, Heinz‐Jürgen
Junge, Wolfgang
Brandt, Roland
author Weissmann, Carina
Reyher, Hans‐Jürgen
Gauthier, Anne
Steinhoff, Heinz‐Jürgen
Junge, Wolfgang
Brandt, Roland
spellingShingle Weissmann, Carina
Reyher, Hans‐Jürgen
Gauthier, Anne
Steinhoff, Heinz‐Jürgen
Junge, Wolfgang
Brandt, Roland
Traffic
Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
Cell Biology
Genetics
Molecular Biology
Biochemistry
Structural Biology
author_sort weissmann, carina
spelling Weissmann, Carina Reyher, Hans‐Jürgen Gauthier, Anne Steinhoff, Heinz‐Jürgen Junge, Wolfgang Brandt, Roland 1398-9219 1600-0854 Wiley Cell Biology Genetics Molecular Biology Biochemistry Structural Biology http://dx.doi.org/10.1111/j.1600-0854.2009.00977.x <jats:p> <jats:bold>During the development of neurons, the microtubule‐associated tau proteins show a graded proximo‐distal distribution in axons. In tauopathies such as Alzheimer's disease, tau accumulates in the somatodendritic compartment. To scrutinize the determinants of tau's distribution and motion, we constructed photoactivatable green fluorescent protein (GFP)‐tagged tau fusion proteins and recorded their distribution after focal activation in living cells. Simulation showed that the motion of tau was compatible with diffusion/reaction as opposed to active transport/reaction. Effective diffusion constants of 0.7–0.8 μm<jats:sup>2</jats:sup>/second were calculated in neurites of PC12 cells and primary cortical neurons. Furthermore, tau's amino terminal projection domain mediated binding and enrichment of tau at distal neurites indicating that the tip of a neurite acts as an adsorber trapping tau protein. Treatment with taxol, incorporation of disease‐related tau modifications, experimentally induced hyperphosphorylation and addition of preaggregated amyloid β peptides (Aβ) increased the effective diffusion constant compatible with a decreased binding to microtubules. Distal enrichment was present after taxol treatment but was suppressed at disease‐relevant conditions. The data suggest that (i) dynamic binding of tau to microtubules and diffusion along microtubules and (ii) trapping at the tip of a neurite both contribute to its distribution during development and disease.</jats:bold> </jats:p> Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons Traffic
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title Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_unstemmed Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_full Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_fullStr Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_full_unstemmed Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_short Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_sort microtubule binding and trapping at the tip of neurites regulate tau motion in living neurons
topic Cell Biology
Genetics
Molecular Biology
Biochemistry
Structural Biology
url http://dx.doi.org/10.1111/j.1600-0854.2009.00977.x
publishDate 2009
physical 1655-1668
description <jats:p> <jats:bold>During the development of neurons, the microtubule‐associated tau proteins show a graded proximo‐distal distribution in axons. In tauopathies such as Alzheimer's disease, tau accumulates in the somatodendritic compartment. To scrutinize the determinants of tau's distribution and motion, we constructed photoactivatable green fluorescent protein (GFP)‐tagged tau fusion proteins and recorded their distribution after focal activation in living cells. Simulation showed that the motion of tau was compatible with diffusion/reaction as opposed to active transport/reaction. Effective diffusion constants of 0.7–0.8 μm<jats:sup>2</jats:sup>/second were calculated in neurites of PC12 cells and primary cortical neurons. Furthermore, tau's amino terminal projection domain mediated binding and enrichment of tau at distal neurites indicating that the tip of a neurite acts as an adsorber trapping tau protein. Treatment with taxol, incorporation of disease‐related tau modifications, experimentally induced hyperphosphorylation and addition of preaggregated amyloid β peptides (Aβ) increased the effective diffusion constant compatible with a decreased binding to microtubules. Distal enrichment was present after taxol treatment but was suppressed at disease‐relevant conditions. The data suggest that (i) dynamic binding of tau to microtubules and diffusion along microtubules and (ii) trapping at the tip of a neurite both contribute to its distribution during development and disease.</jats:bold> </jats:p>
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author Weissmann, Carina, Reyher, Hans‐Jürgen, Gauthier, Anne, Steinhoff, Heinz‐Jürgen, Junge, Wolfgang, Brandt, Roland
author_facet Weissmann, Carina, Reyher, Hans‐Jürgen, Gauthier, Anne, Steinhoff, Heinz‐Jürgen, Junge, Wolfgang, Brandt, Roland, Weissmann, Carina, Reyher, Hans‐Jürgen, Gauthier, Anne, Steinhoff, Heinz‐Jürgen, Junge, Wolfgang, Brandt, Roland
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description <jats:p> <jats:bold>During the development of neurons, the microtubule‐associated tau proteins show a graded proximo‐distal distribution in axons. In tauopathies such as Alzheimer's disease, tau accumulates in the somatodendritic compartment. To scrutinize the determinants of tau's distribution and motion, we constructed photoactivatable green fluorescent protein (GFP)‐tagged tau fusion proteins and recorded their distribution after focal activation in living cells. Simulation showed that the motion of tau was compatible with diffusion/reaction as opposed to active transport/reaction. Effective diffusion constants of 0.7–0.8 μm<jats:sup>2</jats:sup>/second were calculated in neurites of PC12 cells and primary cortical neurons. Furthermore, tau's amino terminal projection domain mediated binding and enrichment of tau at distal neurites indicating that the tip of a neurite acts as an adsorber trapping tau protein. Treatment with taxol, incorporation of disease‐related tau modifications, experimentally induced hyperphosphorylation and addition of preaggregated amyloid β peptides (Aβ) increased the effective diffusion constant compatible with a decreased binding to microtubules. Distal enrichment was present after taxol treatment but was suppressed at disease‐relevant conditions. The data suggest that (i) dynamic binding of tau to microtubules and diffusion along microtubules and (ii) trapping at the tip of a neurite both contribute to its distribution during development and disease.</jats:bold> </jats:p>
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spelling Weissmann, Carina Reyher, Hans‐Jürgen Gauthier, Anne Steinhoff, Heinz‐Jürgen Junge, Wolfgang Brandt, Roland 1398-9219 1600-0854 Wiley Cell Biology Genetics Molecular Biology Biochemistry Structural Biology http://dx.doi.org/10.1111/j.1600-0854.2009.00977.x <jats:p> <jats:bold>During the development of neurons, the microtubule‐associated tau proteins show a graded proximo‐distal distribution in axons. In tauopathies such as Alzheimer's disease, tau accumulates in the somatodendritic compartment. To scrutinize the determinants of tau's distribution and motion, we constructed photoactivatable green fluorescent protein (GFP)‐tagged tau fusion proteins and recorded their distribution after focal activation in living cells. Simulation showed that the motion of tau was compatible with diffusion/reaction as opposed to active transport/reaction. Effective diffusion constants of 0.7–0.8 μm<jats:sup>2</jats:sup>/second were calculated in neurites of PC12 cells and primary cortical neurons. Furthermore, tau's amino terminal projection domain mediated binding and enrichment of tau at distal neurites indicating that the tip of a neurite acts as an adsorber trapping tau protein. Treatment with taxol, incorporation of disease‐related tau modifications, experimentally induced hyperphosphorylation and addition of preaggregated amyloid β peptides (Aβ) increased the effective diffusion constant compatible with a decreased binding to microtubules. Distal enrichment was present after taxol treatment but was suppressed at disease‐relevant conditions. The data suggest that (i) dynamic binding of tau to microtubules and diffusion along microtubules and (ii) trapping at the tip of a neurite both contribute to its distribution during development and disease.</jats:bold> </jats:p> Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons Traffic
spellingShingle Weissmann, Carina, Reyher, Hans‐Jürgen, Gauthier, Anne, Steinhoff, Heinz‐Jürgen, Junge, Wolfgang, Brandt, Roland, Traffic, Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons, Cell Biology, Genetics, Molecular Biology, Biochemistry, Structural Biology
title Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_full Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_fullStr Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_full_unstemmed Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_short Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
title_sort microtubule binding and trapping at the tip of neurites regulate tau motion in living neurons
title_unstemmed Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
topic Cell Biology, Genetics, Molecular Biology, Biochemistry, Structural Biology
url http://dx.doi.org/10.1111/j.1600-0854.2009.00977.x