Mutations in tau reduce its microtubule binding properties in intact cells and affect its phosphorylation

FEBS Letters

Lovestone, S.²  Van Slegtenhorst, M.¹  Ko, L.¹  Hutton, M.¹  Dayanandan, R.²  Anderton, B.H.²  Brion, J.-P.³  Mack, T.G.A.²  Leroy, K.³  Yen, S.-H.¹ 

[1] The Birdsall Research Building, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA;Departments of Neuroscience and Old Age Psychiatry, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK;Laboratory of Pathology and electron Microscopy, Univeristé Libre de Bruxelles, 808, route de Lennik, Bldg C-10, 1070 Brussels, Belgium

关键词: Tau;    Fronto-temporal degeneration;    Mutation;    Microtubule;    GSK-3;   

DOI  :  10.1016/S0014-5793(99)00222-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown