Anionic micelles and vesicles induce tau fibrillization in vitro.
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 full-length tau protein, arachidonic acid, and a series of straight chain 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.
Biophysics Program and Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA.
Carmen N
CN
Chirita
Mihaela
M
Necula
Jeff
J
Kuret
D000544:Alzheimer Disease / Q000378:metabolism; D000838:Anions; D016718:Arachidonic Acid / Q000378:metabolism; D002412:Cations; D003902:Detergents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism; D008823:Micelles; D008854:Microscopy, Electron; D010770:Phosphotransferases / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry*
D000838:Anions; D002412:Cations; D003902:Detergents; D005227:Fatty Acids; D008024:Ligands; D008055:Lipids; D008081:Liposomes; D008823:Micelles; D000644:Quaternary Ammonium Compounds; D011994:Recombinant Proteins; D016875:tau Proteins; D016718:Arachidonic Acid; D010770:Phosphotransferases