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

Cell Adh Migr. 2016 May 3;10(3):237-47. doi: 10.4161/19336918.2014.994916. Epub 2016 May 9.

Abstract

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.

Keywords: CaMKII; GluR1; LTD; LTP; Wip1; hippocampus.

MeSH terms

  • Aging / metabolism
  • Animals
  • CA1 Region, Hippocampal / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cell Membrane / metabolism
  • Long-Term Potentiation*
  • Long-Term Synaptic Depression*
  • Male
  • Mice, Inbred C57BL
  • Phosphorylation
  • Protein Phosphatase 2C / deficiency
  • Protein Phosphatase 2C / metabolism*
  • Receptors, AMPA / metabolism

Substances

  • Receptors, AMPA
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Ppm1d protein, mouse
  • Protein Phosphatase 2C
  • glutamate receptor ionotropic, AMPA 1