Wip1 phosphatase modulates both long-term potentiation and long-term depression through the dephosphorylation of CaMKII

Zhi-Yong He, Wei-Yan Hu, Ming Zhang, Zara Zhuyun Yang, Hong-Mei Zhu, Da Xing, Quan-Hong Ma, Zhi-Cheng Xiao

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3 Citations (Scopus)


Synaptic plasticity is an important mechanism that underlies learning and cognition. Protein phosphorylation by kinases and dephosphorylation by phosphatases play critical roles in the activity-dependent alteration of synaptic plasticity. In this study, we report that Wip1, a protein phosphatase, is essential for long-term potentiation (LTP) and long-term depression (LTD) processes. Wip1-deletion suppresses LTP and enhances LTD in the hippocampus CA1 area. Wip1 deficiency-induced aberrant elevation of CaMKII T286/287 and T305 phosphorylation underlies these dysfunctions. Moreover, we showed that Wip1 modulates CaMKII dephosphorylation. Wip1-/- mice exhibit abnormal GluR1 membrane expression, which could be reversed by the application of a CaMKII inhibitor, indicating that Wip1/CaMKII signaling is crucial for synaptic plasticity. Together, our results demonstrate that Wip1 phosphatase plays a vital role in regulating hippocampal synaptic plasticity by modulating the phosphorylation of CaMKII.
Original languageEnglish
Pages (from-to)237-247
Number of pages11
JournalCell Adhesion and Migration
Issue number3
Publication statusPublished - 2016


  • CaMKII
  • GluR1
  • hippocampus
  • LTD
  • LTP
  • Wip1

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