Dephosphorylation of tau protein by calcineurin triturated into neural living cells.
Alzheimer disease and related dementia are characterized by the presence of hyperphosphorylated tau aggregated into filaments. The role of tau phosphorylation in the fibrillogenesis has not yet been unraveled. Therefore, it is important to know which phosphatases can dephosphorylate tau protein in vivo. The effect of recombinant purified calcineurin (CN(PP2B)) and several calcineurin mutants on tau phosphorylation was studied in two neuronal like cell lines PC12 and SH-SY5Y. The modulation of tau phosphorylation at Serl99/Ser202, Ser396/Ser404, Ser262/Ser356, and Thr181 sites was examined in these cell lines using the phosphorylation state-dependent antitau antibodies Tau 1, PHF1, 12E8, and AT270. The results have shown that CN directly dephosphorylates all of those sites of tau protein. Recombinant calcineurin introduced into cells that have previously been treated with okadaic acid and cyclosporin A, which are inhibitors of phosphatases (PP1/PP2A and PP2B), has a direct effect on the phosphorylation status on all phosphorylation sites studied. We conclude that calcineurin is (besides PP2A) a important modulator of tau phosphorylation in vivo.
Wei
Qun
Q
Department of Biochemistry and Molecular Biology, Beijing Normal University, People's Republic of China. weiq@bnu.edu.cn
Holzer
Max
M
Brueckner
Martina K
MK
Liu
Yu
Y
Arendt
Thomas
T
D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma; D019319:Okadaic Acid / Q000494:pharmacology; D016716:PC12 Cells; D010673:Pheochromocytoma; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D021122:Protein Subunits; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D021122:Protein Subunits; D011994:Recombinant Proteins; D016875:tau Proteins; D019319:Okadaic Acid; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases