GSK-3 dependent phosphoepitopes recognized by PHF-1 and AT-8 antibodies are present in different tau isoforms.
It is widely known that the tau protein that forms the aggregates found in tauopathies like Alzheimer's disease (AD) is hyperphosphorylated. Many of the sites that are hyperphosphorylated in AD can also be found phosphorylated in non-pathological control brains, although to a lesser extend. Among the different kinases that are able to phosphorylate tau in these sites, GSK-3 has emerged as a key effector of AD pathogenesis in view of its interaction with many of the proteins involved in the ethiology of AD. In this work, we have tested if control samples show only a decrease in the amount of phosphorylated tau molecules, or if the phosphorylation at different sites occurs in different tau isoforms, whereas in the pathological situation a single tau isoform is modified simultaneously at the different sites. Our results indicate that the second possibility takes place and that the differences in the phosphorylation of different tau isoforms could be due to a different subcellular distribution of these different tau isoforms in a neuron.
Hernández
Félix
F
Centro de Biología Molecular "Severo Ochoa", CSIC/UAM, Fac. Ciencias Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Lucas
José J
JJ
Cuadros
Raquel
R
Avila
Jesús
J
D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002451:Cell Compartmentation / Q000502:physiology; D045744:Cell Line, Tumor; D000939:Epitopes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D008094:Lithium / Q000494:pharmacology; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; C085349:PHF-1 monoclonal antibody; D020033:Protein Isoforms; D016875:tau Proteins; D008094:Lithium; D038362:Glycogen Synthase Kinase 3