Zinc Binding Directly Regulates Tau Toxicity Independent of Tau Hyperphosphorylation
Zinc Binding Directly Regulates Tau Toxicity Independent of Tau Hyperphosphorylation
复制标题
锌结合直接调节 Tau 毒性，与 Tau 过度磷酸化无关
DOI：
10.1016/j.celrep.2014.06.047
复制
发表时间：
2014-08-07
期刊：
影响因子：
8.8
通讯作者：
Zhou, Bing
中科院分区：
文献类型：
--
作者：
Huang, Yunpeng;Wu, Zhihao;Zhou, Bing
Tau hyperphosphorylation is thought to underlie tauopathy. Working in a Drosophila tauopathy model expressing a human Tau mutant (hTauR406W, or Tau(star)), we show that zinc contributes to the development of Tau toxicity through two independent actions: by increasing Tau phosphorylation and, more significantly, by directly binding to Tau. Elimination of zinc binding through amino acid substitution of Cys residues has a minimal effect on phosphorylation levels yet essentially eliminates Tau toxicity. The toxicity of the zinc-binding-deficient mutant Tau(star) (Tau(star)C2A) and overexpression of native Drosophila Tau, also lacking the corresponding zinc-binding Cys residues, are largely impervious to zinc concentration. Importantly, restoration of zinc-binding ability to Tau(star) by introduction of a zinc-binding residue (His) into the original Cys positions restores zinc-responsive toxicities in proportion to zinc-binding affinities. These results indicate zinc binding is a substantial contributor to tauopathy and have implications for therapy development.
