Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A.
Recently, we reported that a pool of protein phosphatase 2A (PP2A) is associated with microtubules. Here, we demonstrate that specific isoforms of PP2A bind and dephosphorylate the neuronal microtubule-associated protein tau. Coexpression of tau and SV40 small t, a specific inhibitor of PP2A, in CV-1, NIH 3T3, or NT2 cells induced the phosphorylation of tau at multiple sites, including Ser-199, Ser-202, Thr-205, Ser-396, and Ser-404. Immunofluorescent and biochemical analyses revealed that hyperphosphorylation correlated with dissociation of tau from microtubules and a loss of tau-induced microtubule stabilization. Taken together, these results support the hypothesis that PP2A controls the phosphorylation state of tau in vivo.
Sontag
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E
Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
Nunbhakdi-Craig
V
V
Lee
G
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Bloom
G S
GS
Mumby
M C
MC
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D004355:Drug Stability; D000939:Epitopes; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D016875:tau Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D000939:Epitopes; D007527:Isoenzymes; D016875:tau Proteins; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2