14-3-3ζ Facilitates GSK3β-catalyzed tau phosphorylation in HEK-293 cells by a mechanism that requires phosphorylation of GSK3β on Ser9

Hyperphosphorylated tau is the prominent component of paired helical filaments, which are the major component of neurofibrillary tangles associated with Alzheimer's disease (AD). Glycogen synthase kinase 3 beta (GSK3 beta) is implicated to phosphorylate tau in normal and AD brain. Previously, we isolated a large multiprotein complex containing tau, Ser(9)-phosphorylated GSK3 beta and 14-3-3 zeta from bovine brain microtubules. We showed that within the complex, 14-3-3 zeta binds to tau and GSK3 beta and mediates GSK3 beta-catalyzed tau phosphorylation. A recent report however indicated that 14-3-3 zeta does not bind to tau or GSK3 beta and does not increase tau phosphorylation by GSK3 beta in cell models [T.A. Matthews, G.V.W. Johnson, Neurosci. Lett. 384 (2005) 211-216]. In the current study we have thoroughly analyzed the binding of 14-3-3 zeta with tau and GSK3 beta and evaluated the effect of 14-3-3 beta on tau phosphorylation by GSK3 beta in HEK-293 cells. We found that 14-3-3 zeta binds to tau and Serophosphorylated GSK3 beta. Nonphosphorylated GSK3 beta phosphorylates tau without being influenced by 14-3-3 zeta. Ser(9)-phosphorylated GSK3 beta on the other hand phosphorylates tau significantly only in the presence of 14-3-3 zeta. Our data demonstrate that 14-3-3C mediates tau phosphorylation by Ser(9)-phosphorylated GSK3 beta in HEK-293 cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.