Disulfide-cross-linked tau and MAP2 homodimers readily promote microtubule assembly.
The neuronal proteins Tau and MAP2 use homologous C-terminal MT-binding regions (MTBRs) to interact with microtubules, F-actin, and intermediate filaments. Although Tau-MTBR is the principal component of pronase-treated Alzheimer paired helical filaments, both Tau and MAP2 form filaments in vitro from disulfide-linked homodimers. That the critical thiol lies within a domain needed for MT binding raised the question: Does disulfide formation block Tau-Tau or MAP2-MAP2 dimer binding to microtubules, thereby acting to divert dimers toward filament formation? We now report that cross-linked Tau and MAP2 homodimers readily promote tubulin polymerization and that monomer and dimer affinity for MTs is surprisingly similar. Therefore, disulfide cross-bridging into homodimers is unlikely to be a drive force for filament formation in Alzheimer's disease.
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Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Health Science Center, Gainesville 32610-0245, USA.
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D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D008870:Microtubules / Q000737:chemistry* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D014404:Tubulin / Q000737:chemistry / Q000648:ultrastructure; D016875:tau Proteins / Q000737:chemistry*
D004220:Disulfides; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D016875:tau Proteins