Anionic Micelles and Vesicles Induce Tau Fibrillizationin Vitro

Carmen N. Chirita, Mihaela Necula, Jeff Kuret
2003 Journal of Biological Chemistry  
Alzheimer's disease is defined in part by the intraneuronal accumulation of filaments comprised of the microtubule-associated protein tau. In vitro, fibrillization of recombinant tau can be induced by treatment with various agents, including phosphotransferases, polyanionic compounds, and fatty acids. Here we characterize the structural features required for the fatty acid class of tau fibrillization inducer using recombinant fulllength tau protein, arachidonic acid, and a series of straight
more » ... in anionic, cationic, and nonionic detergents. Induction of measurable tau fibrillization required an alkyl chain length of at least 12 carbons and a negative charge consisting of carboxylate, sulfonate, or sulfate moieties. All detergents and fatty acids were micellar at active concentrations, due to a profound, taudependent depression of their critical micelle concentrations. Anionic surfaces larger than detergent micelles, such as those supplied by phosphatidylserine vesicles, also induced tau fibrillization with resultant filaments originating from their surface. These data suggest that anionic surfaces presented as micelles or vesicles can serve to nucleate tau fibrillization, that this mechanism underlies the activity of fatty acid inducers, and that anionic membranes may serve this function in vivo. 1 The abbreviations used are: CMC, critical micelle concentration; AA, arachidonic acid.
doi:10.1074/jbc.m301663200 pmid:12730214 fatcat:iva4ixvxpvh5vhk3mgirgvuioq