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 tub ulin alone. Urea at 200 mM blocks tubulin assembly caused by tau, but this inhibition can be reversed by an equal amount of TMAO. Besides TM AO, betaine, another natural osmolyte, was found to have the same effe cts on MT as TMAO. On the contrary, glycerol (a carbohydrate osmolyte) and glycine tan amino acid osmolyte) do not increase tau-induced MT a ssembly. The mechanism by which TMAO and betaine enhance tau's effecti veness is not known, but physical studies suggest that the secondary s tructure of tau is not appreciably changed by 200 mM TMAO. This is the first report showing that natural osmolytes, TMAO and betaine, at a n ear physiological concentration are able to stimulate tau-induced tubu lin assembly. (C) 1998 academic Press.