Three- and Four-repeat Tau Coassemble into Heterogeneous Filaments
نویسندگان
چکیده
منابع مشابه
Three Repeat Isoforms of Tau Inhibit Assembly of Four Repeat Tau Filaments
Tauopathies are defined by assembly of the microtubule associated protein tau into filamentous tangles and classified by the predominant tau isoform within these aggregates. The major isoforms are determined by alternative mRNA splicing of exon 10 generating tau with three (3R) or four (4R) approximately 32 amino acid imperfect repeats in the microtubule binding domain. In normal adult brains t...
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Tau pathology in Alzheimer's disease is intimately linked to the deposition of proteinacious filaments, which akin to infectious prions, have been proposed to spread via seeded conversion. Here we use double electron-electron resonance (DEER) spectroscopy in combination with extensive computational analysis to show that filaments of three- (3R) and four-repeat (4R) tau are conformationally dist...
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Tau protein is present in six different splice forms in the human brain and interacts with microtubules via either 3 or 4 microtubule binding repeats. An increased ratio of 3 repeat to 4 repeat isoforms is associated with neurodegeneration in inherited forms of frontotemporal dementia. Tau over-expression diminishes axonal transport in several systems, but differential effects of 3 repeat and 4...
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Tau exists as six closely related protein isoforms in the adult human brain. These are generated from alternative splicing of a single mRNA transcript and they differ in the absence or presence of two N-terminal and three or four microtubule binding domains. Typically all six isoforms have been considered functionally similar. However, their differential involvement in particular tauopathies ra...
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In Alzheimer's disease and frontotemporal dementias, the microtubule-associated protein Tau forms intracellular paired helical filaments. The filaments can form not only by the full-length human Tau protein, but also by the three repeated (K19) or four repeated (K18) Tau segments. However, of interest, experimentally, K19 can seed K18, but not vice versa. To obtain insight into the cross-seedin...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2010
ISSN: 0021-9258
DOI: 10.1074/jbc.m110.185728