Natural methylamine osmolytes, trimethylamine N-oxide and betaine, increase tau-induced polymerization of microtubules.

The natural osmolyte trimethylamine N-oxide (TMAO) at 200 mM increases the extent and the rate of formation of polymerized microtubule (MT) complex caused by tau. TMAO at this concentration has no effect on tubulin alone. Urea at 200 mM blocks tubulin assembly caused by tau, but this inhibition can be reversed by an equal amount of TMAO. Besides TMAO, betaine, another natural osmolyte, was found to have the same effects on MT as TMAO. On the contrary, glycerol (a carbohydrate osmolyte) and glycine (an amino acid osmolyte) do not increase tau-induced MT assembly. The mechanism by which TMAO and betaine enhance tau's effectiveness is not known, but physical studies suggest that the secondary structure of tau is not appreciably changed by 200 mM TMAO. This is the first report showing that natural osmolytes, TMAO and betaine, at a near physiological concentration are able to stimulate tau-induced tubulin assembly.