The natural osmolyte trimethylamine N‐oxide (TMAO) restores the ability of mutant tau to promote microtubule assembly

FEBS Letters

Crowther, R.Anthony¹  Smith, Michael J¹  Goedert, Michel¹ 

[1] Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

关键词: Tau protein mutation;    Frontotemporal dementia;    Phosphorylation;    Microtubule assembly;    Trimethylamine N-oxide;   

DOI  :  10.1016/S0014-5793(00)02169-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Coding region and intronic mutations in the gene for microtubule-associated protein tau cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Most coding region mutations effect a reduced ability of tau protein to interact with microtubules and lead to the formation of a filamentous pathology made of hyperphosphorylated tau. Here we show that trimethylamine N-oxide (TMAO) restores the ability of tau with FTDP-17 mutations to promote microtubule assembly. To mimic phosphorylation, serine and threonine residues in tau were singly or multiply mutated to glutamic acid, resulting in a reduced ability of tau to promote microtubule assembly. With the exception of the most heavily substituted protein (27 glutamic acid residues), TMAO increased the ability of mutant tau to promote microtubule assembly. However, it had no significant effect on heparin-induced assembly of tau into filaments.

【 授权许可】

Unknown