Optimization of in vitro conditions to study the arachidonic acid induction of 4R isoforms of the microtubule-associated protein tau

2017 ◽  
pp. 65-88 ◽  
Author(s):  
Yamini Mutreja ◽  
Truman C. Gamblin
Keyword(s):  
Arachidonic Acid ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau

scholarly journals Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Wenjuan Zhang ◽  
Benjamin Falcon ◽  
Alexey G Murzin ◽  
Juan Fan ◽  
R Anthony Crowther ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Neurodegenerative Diseases ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
The Third ◽  
In Vitro Assembly ◽  
Immuno Electron Microscopy ◽  
Structural Versatility ◽  
Filamentous Inclusions

Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range of neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer’s and Pick’s diseases. Here, we used cryo- and immuno- electron microscopy to characterise filaments that were assembled from recombinant full-length human tau with four (2N4R) or three (2N3R) microtubule-binding repeats in the presence of heparin. 2N4R tau assembles into multiple types of filaments, and the structures of three types reveal similar ‘kinked hairpin’ folds, in which the second and third repeats pack against each other. 2N3R tau filaments are structurally homogeneous, and adopt a dimeric core, where the third repeats of two tau molecules pack in a parallel manner. The heparin-induced tau filaments differ from those of Alzheimer’s or Pick’s disease, which have larger cores with different repeat compositions. Our results illustrate the structural versatility of amyloid filaments, and raise questions about the relevance of in vitro assembly.

scholarly journals Microtubule-associated protein tau is essential for long-term depression in the hippocampus

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130144 ◽  
Author(s):  
Tetsuya Kimura ◽  
Daniel J. Whitcomb ◽  
Jihoon Jo ◽  
Philip Regan ◽  
Thomas Piers ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Principal Component ◽  
Synaptic Function ◽  
Glycogen Synthase Kinase 3 ◽  
Long Term Depression ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau

The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro , an effect that was replicated by RNAi knockdown of tau in vitro . We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.

scholarly journals Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases

2018 ◽  
Author(s):  
Wenjuan Zhang ◽  
Benjamin Falcon ◽  
Alexey G. Murzin ◽  
Juan Fan ◽  
R. Anthony Crowther ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Neurodegenerative Diseases ◽  
Microtubule Binding ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
The Third ◽  
Negative Stain ◽  
Different Types ◽  
Filamentous Inclusions

AbstractThe assembly of microtubule-associated protein tau into abundant filamentous inclusions underlies a range of neurodegenerative diseases. The finding that tau filaments adopt different conformations in Alzheimer’s and Pick’s diseases raises the question of what kinds of structures of tau filaments form in vitro. Here, we used electron cryo-microscopy (cryo-EM) and negative-stain immuno-gold electron microscopy (immuno-EM) to characterise filaments that were assembled from recombinant full-length human tau with four (2N4R) or three (2N3R) microtubule-binding repeats in the presence of heparin. 4R tau assembles into at least four different types of filaments. Cryo-EM structures of three types of 4R filaments reveal similar “kinked hairpin” folds, in which the second and third repeats pack against each other. 3R tau filaments are structurally homogeneous, and adopt a dimeric core, where the third repeats of two tau molecules pack against each other in a parallel, yet asymmetric, manner. None of the heparin-induced tau filaments resemble those of Alzheimer’s or Pick’s disease, which have larger cores with different repeat compositions. Our results indicate that tau filaments are structurally versatile, and raise questions about the relevance of in vitro assembled amyloids.

Microtubule-associated protein tau and in vitro paclitaxel sensitivity in primary breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20088-20088
Author(s):  
M. Schmidt ◽  
E. Bremer ◽  
A. Victor ◽  
M. Gehrmann ◽  
J. G. Hengstler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Area Under The Curve ◽  
Wilcoxon Test ◽  
Test Results ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
Er Positive ◽  
Spearman’S Correlation

20088 Background: Paclitaxel has an important role in the adjuvant therapy of primary breast cancer. Recently, microtubule-associated protein tau was described as a marker of paclitaxel sensitivity. We attempted to validate these findings in vitro utilizing the ATP tumorchemosensitivity assay (ATP-TCA). Methods: The in vitro drug sensitivity to paclitaxel was evaluated in 48 fresh primary breast cancer specimens using the ATP-TCA. ATP-TCA results were analysed using the area under the curve (AUC) of growth inhibition. These results were correlated with the expression of tau mRNA measured by quantitative RT-PCR (Spearman’s correlation coefficient). Tau was also compared between progesterone receptor (PgR) positive and negative and estrogen receptor (ER) positive and negative tumors, respectively (Wilcoxon test). Results: The correlation of tau with the AUC for paclitaxel was weak (r = −0.20) and disappeared when considering PgR positive and negative tumors separately (r = −0.004 and r = −0.048, respectively). Tau was found to be differentially expressed between PgR positive and negative as well as between ER positive and negative tumors (p < 0.0005 in both tests). Conclusions: The expression of tau does not show independent predictive value for the in vitro paclitaxel sensitivity in primary breast cancer. No significant financial relationships to disclose.

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