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In vitro evidence has suggested a change in the ability of tau bearing mutations associated with fronto-temporal dementia to promote microtubule assembly. We have used a cellular assay to quantitate the effect of both isoform differences and mutations on the physiological function of tau. Whilst all variants of tau bind to microtubules, microtubule extension is reduced in cells transfected with 3-relative to 4-repeat tau. Mutations reduce microtubule extension with the P301L mutation having a greater effect than the V337M mutation. The R406W mutation had a small effect on microtubule extension but, surprisingly, tau with this mutation was less phosphorylated in intact cells than the other variants.

Type

Journal article

Journal

FEBS Lett

Publication Date

12/03/1999

Volume

446

Pages

228 - 232

Keywords

Animals, CHO Cells, Calcium-Calmodulin-Dependent Protein Kinases, Cricetinae, Glycogen Synthase Kinase 3, Microtubules, Mutagenesis, Site-Directed, Neurons, Phosphorylation, tau Proteins