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

Mutations in tau reduce its microtubule binding properties in intact cells and affect its phosphorylation
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DOI:
10.1016/s0014-5793(99)00222-7
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发表时间:
1999-03-12
期刊:
影响因子:
3.5
通讯作者:
Lovestone, S
Lovestone, S
中科院分区:
生物学3区
文献类型:
--
作者:
Dayanandan, R;Van Slegtenhorst, M;Lovestone, S

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体外证据表明,与额颞叶痴呆相关的tau蛋白携带突变促进微管组装的能力发生了变化。我们已经使用细胞测定来定量同种型差异和突变对tau的生理功能的影响。虽然tan的所有变体都结合微管,但微管延伸在用3-相对于4-重复tau转染的细胞中减少。突变减少微管延伸,其中P301 L突变比V337 M突变具有更大的影响。R406 W突变对微管延伸的影响很小,但令人惊讶的是,具有这种突变的tau在完整细胞中的磷酸化程度低于其他变体。(C)1999年欧洲生物化学学会联合会。
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 tan 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. (C) 1999 Federation of European Biochemical Societies.