Specific macromolecular interactions between tau and the microtubule system.
The microtubule-associated protein Tau, a major component of brain microtubules, shares common repeated C-terminal sequences with the high molecular-weight protein MAP-2. It has been shown that tau peptides V187-G204 and V218-G235, representing two main repeats, induced brain tubulin assembly in a concentration-dependent fashion. The specific roles of these repeats in the interaction of tau with microtubules, and its antigenic nature were investigated using synthetic tau peptides and site-directed monoclonal antibodies. Tau peptides appeared to compete with MAP-2 incorporation into assembled microtubules. The interactions of the tau fragments with beta-tubulin peptides bearing the tau binding domain on tubulin were analyzed by fluorescence spectroscopy. The specificity of the binding was further demonstrated by the reactivity of tau and the tau peptides with a monoclonal anti-idiotypic antibody produced after immunization with the beta-II(422-434) tubulin peptide, as assessed by enzyme-linked immunoassay. Western blots confirmed the interaction of tau with the monoclonal antibody. In addition, immunoassays revealed a competition between the MAP-reacting monoclonal antibody and the tubulin peptide beta-II(422-434) for their interaction with the tau molecule.
Farías
G A
GA
Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago.
Vial
C
C
Maccioni
R B
RB
D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic; D001665:Binding Sites; D001667:Binding, Competitive; D001923:Brain Chemistry; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D014404:Tubulin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D010446:Peptide Fragments; D014404:Tubulin; D016875:tau Proteins