Wip1 phosphatase modulates both long-term potentiation and long-term depression through the dephosphorylation of CaMKII |
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| Authors: | Zhi-Yong He Wei-Yan Hu Ming Zhang Zara Zhuyun Yang Hong-mei Zhu |
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| Affiliation: | 1. MOE Key Laboratory of Laser Life Science &2. Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China;3. The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China;4. Department of Anatomy and Developmental Biology, Monash University, Clayton, Melbourne, Australia;5. The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China;6. School of Pharmaceutical Science &7. Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, China |
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| 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. |
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| Keywords: | CaMKII GluR1 hippocampus LTD LTP Wip1 |
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