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The natural osmolyte trimethylamine N ‐oxide (TMAO) restores the ability of mutant tau to promote microtubule assembly
Author(s) -
Smith Michael J,
Crowther R.Anthony,
Goedert Michel
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02169-4
Subject(s) - tau protein , mutant , microtubule , chemistry , microbiology and biotechnology , phosphorylation , biochemistry , threonine , mutation , serine , biology , gene , alzheimer's disease , medicine , disease , pathology
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.