Detection of Phosphorylated Ser in Fetal Tau, Adult Tau, and Paired Helical Filament Tau

• Published in: The Journal of biological chemistry Vol. 270; no. 32; p. 18917
• Main Authors: Peter Seubert, Madhumalti Mawal-Dewan, Robin Barbour, Ross Jakes, Michel Goedert, Gail V. W. Johnson, Joel M. Litersky, Dale Schenk, Ivan Lieberburg, John Q. Trojanowski, Virginia M.-Y. Lee
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 11-08-1995
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.32.18917

Paired helical filaments (PHFs) are the major structural elements of Alzheimer's disease neurofibrillary lesions, and these
filaments are formed from hyperphosphorylated brain tau known as PHF-tau. Recent studies showed that many previously identified
phosphorylated residues in PHF-tau also are phosphate acceptor sites in fetal and rapidly processed adult brain tau. However,
Ser has been suggested to be uniquely phosphorylated in PHF-tau and a key regulator of the binding of tau to microtubules. For
these reasons, we generated a monoclonal antibody (12E8) specific for phosphorylated Ser and showed that 12E8 binds to PHF-tau, rat and human fetal brain tau, as well as to rapidly processed adult rat and biopsy-derived
human brain tau. Further, phosphorylation at Ser was developmentally regulated, and endogenous brain phosphatases rapidly dephosphorylated Ser in biopsy-derived brain tau isolates. Finally, the phosphorylation of Ser did not eliminate the binding of tau to microtubules. Thus, we speculate that the binding of tau to microtubules is regulated
by phosphorylation at multiple sites and that the generation of PHF-tau in Alzheimer's disease results from the reduced efficiency
of phosphatases leading to the incremental accumulation of hyperphosphorylated tau.