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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Smith MJ,Crowther RA,Goedert M

doi

10.1016/s0014-5793(00)02169-4

keywords:

subject

Has Abstract

pub_date

2000-11-10 00:00:00

pages

265-70

issue

3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(00)02169-4

journal_volume

484

pub_type

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