1Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, China
2Key Laboratory of Neurological Disease, Ministry of Education, and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China
4The Third Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha 410013, China
Corresponding authors: Rong Liu and Qi-Fa Ye. E-mail: rong.liu@mail.hust.edu.cn, yqf_china@163.com

Abstract 

Zinc induces protein phosphatase 2A (PP2A) inactivation and tau hyperphosphorylation through PP2A (tyrosine 307) phosphorylation in cells and the brain, but whether Zn2+ has a direct inhibitory effect on PP2A is not clear. Here we explored the effect of Zn2+ on PP2A and their direct interaction in vitro. The results showed that Zn2+ mimicked the inhibitory effect of okadaic acid on protein phosphatase and prevented tau dephosphorylation in N2a cell lysates. PP2A activity assays indicated that a low concentration (10 μmol/L) of Zn2+ inhibited PP2A directly. Further Zn2+-IDA-agarose affinity binding assays showed that Zn2+ bound to and inhibited PP2Ac(51-270) but not PP2Ac(1-50) or PP2Ac(271-309). Taken together, Zn2+ inhibits PP2A directly through binding to PP2Ac(51-270) in vitro.

Keywords

zinc; protein phosphatase 2A; direct inhibition

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