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 isofo rms of PP2A bind and dephosphorylate the neuronal microtubule-associat ed protein tau. Coexpression of tau and SV40 small t, a specific inhib itor of PP2A, in CV-1, NIH 3T3, or NT2 cells induced the phosphorylati on 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 mic rotubules and a loss of tau-induced microtubule stabilization. Taken t ogether, these results support the hypothesis that PP2A controls the p hosphorylation state of tau in vivo.