Optimization of in vitro conditions to study the arachidonic acid induction of 4R isoforms of the microtubule-associated protein tau.
Methods Cell Biol
; 141: 65-88, 2017.
Article
en En
| MEDLINE
| ID: mdl-28882312
The microtubule-associated protein tau exists in six different isoforms that accumulate as filamentous aggregates in a wide spectrum of neurodegenerative diseases classified as tauopathies. One potential source of heterogeneity between these diseases could arise from differential tau isoform aggregation. in vitro assays employing arachidonic acid as an inducer of aggregation have been pivotal in gaining an understanding of the longest four repeat tau isoform (2N4R). These approaches have been less successful for modeling the shorter 1N4R and 0N4R tau isoforms in vitro. Through a careful analysis of in vitro conditions for aggregation, we found that the differences in the acidity of tau isoform N-terminal projection domains determine whether tau filaments cluster into larger assemblies in solution. Beyond the potential biological implications of filament clustering, we provide optimized conditions for the arachidonic acid induction of shorter 4R tau isoforms aggregation in vitro that greatly reduce filament clustering and improved modeling results.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácido Araquidónico
/
Proteínas tau
/
Multimerización de Proteína
/
Microtúbulos
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Methods Cell Biol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos