Polymerization of microtubule-associated protein tau under near-physiological conditions.
Neurofibrillary tangles, which form in certain degenerating neurons in the brains of patients with Alzheimer's disease, are amassed from filaments having a straight or paired helical morphology. Solubilization of these filaments reveals that they are composed of the microtubule-associated protein tau. It has not previously been shown, however, that tau will assemble to form filaments of similar morphology under conditions representative of the intracellular environment. We have succeeded in forming such filaments using tau purified from porcine or rat microtubules. The filaments are relatively straight with narrowing at irregular intervals, and are about 10 nm wide, a morphology similar to that of straight filaments seen in Alzheimer's disease neurofibrillary tangles. At tau concentrations of 1-10 microM, in vitro assembly occurs at physiological pH, ionic strength, temperature, and reducing potential, and each one of these factors modulates the reaction. Assembly is judged to be only slowly reversible by the exponential rather than normal distribution of filament lengths, and by the limited disassembly observed under conditions which inhibit polymerization. Tau purified directly from whole brain tissue rather than from microtubules does not polymerize under conditions described in this report.
Wilson
D M
DM
Department of Cell Biology, University of Alabama at Birmingham 35294, USA.
Binder
L I
LI
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D000075065:Elongin; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012313:RNA / Q000096:biosynthesis; D012319:RNA Polymerase II / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D013698:Templates, Genetic; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic
D000075065:Elongin; D014157:Transcription Factors; D012313:RNA; D012319:RNA Polymerase II