Mutations in tau reduce its microtubule binding properties in intact cellsand affect its phosphorylation

In vitro evidence has suggested a change in the ability of tau bearing muta tions associated with fronto-temporal dementia to promote microtubule assem bly. 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 tan bind to microtubules, microtubule extension is reduced in cells transfected with 3-relative to 4-repeat tau, Mutations reduce microtu bule extension with the P301L mutation having a greater effect than the V33 7M mutation. The R406W mutation had a small effect on microtubule extension but, surprisingly, tau with this mutation was less phosphorylated in intac t cells than the other variants. (C) 1999 Federation of European Biochemica l Societies.