Posttranslational modifications of tau in paired helical filaments.
Paired helical filaments (PHF) are fibrillar structures that accumulate in degenerating neurons of AD brain. We have purified their components, PHF-tau and PHF-smear, and analyzed them protein chemically. PHF-tau is abnormally phosphorylated. Although the characteristic of this phosphorylation is similar to that of fetal tau, its extent is higher in PHF-tau. The additional phosphorylation in PHF-tau may cause its loss of microtubule assembly capacity. Our results on the phosphorylation sites suggested that fetal tau and presumably PHF-tau are in vivo substrates of proline-directed protein kinases. PHF-smear consisted largely of the carboxyl-terminal portion of tau and ubiquitin. The ubiquitin-targeted protein was identified as tau in PHF and the conjugation sites were localized to the microtubule-binding region. It is most likely that abnormally phosphorylated full-length tau (PHF-tau) accumulates as PHF, which is then gradually processed from its amino-terminus and followed by ubiquitination.
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
M
M
Morishima
Y
Y
Ihara
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D014452:Ubiquitins / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D014452:Ubiquitins; D016875:tau Proteins