title: Taxol-stabilized microtubules promote the formation of filaments from unmodified full-length Tau in vitro.
abstract: Tau is a neuronal protein that stabilizes the microtubule (MT) network, but it also forms filaments associated with Alzheimer's disease. Understanding Tau-MT and Tau-Tau interactions would help to establish Tau function in health and disease. For many years, literature reports on Tau-MT binding behavior and affinity have remained surprisingly contradictory (e.g., 10-fold variation in Tau-MT affinity). Tau-Tau interactions have also been investigated, but whether MTs might affect Tau filament formation is unknown. We have addressed these issues through binding assays and microscopy. We assessed Tau-MT interactions via cosedimentation and found that the measured affinity of Tau varies greatly, depending on the experimental design and the protein concentrations used. To investigate this dependence, we used fluorescence microscopy to examine Tau-MT binding. Strikingly, we found that Taxol-stabilized MTs promote Tau filament formation without characterized Tau-filament inducers. We propose that these novel Tau filaments account for the incongruence in Tau-MT affinity measurements. Moreover, electron microscopy reveals that these filaments appear similar to the heparin-induced Alzheimer's model. These observations suggest that the MT-induced Tau filaments provide a new model for Alzheimer's studies and that MTs might play a role in the formation of Alzheimer's-associated neurofibrillary tangles.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Aranda R
authors.initials: AR
authors.lastname: Duan
authors.forename: Holly V
authors.initials: HV
authors.lastname: Goodson
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D001667:Binding, Competitive; D015153:Blotting, Western; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology*; D011485:Protein Binding; D050257:Tubulin Modulators / Q000494:pharmacology; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D050257:Tubulin Modulators; D016875:tau Proteins; D006493:Heparin; D017239:Paclitaxel