title: Wip1 phosphatase modulates both long-term potentiation and long-term depression through the dephosphorylation of CaMKII.
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.
authors.affiliation: a MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou , China.|b The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University , Kunming , China.|c Department of Anatomy and Developmental Biology , Monash University , Clayton , Melbourne , Australia.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: He
authors.affiliation: b The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University , Kunming , China.|c Department of Anatomy and Developmental Biology , Monash University , Clayton , Melbourne , Australia.|e School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University , Kunming , China.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Hu
authors.affiliation: b The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University , Kunming , China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: b The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University , Kunming , China.|c Department of Anatomy and Developmental Biology , Monash University , Clayton , Melbourne , Australia.
authors.forename: Zara Zhuyun
authors.initials: ZZ
authors.lastname: Yang
authors.affiliation: b The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University , Kunming , China.|c Department of Anatomy and Developmental Biology , Monash University , Clayton , Melbourne , Australia.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhu
authors.affiliation: a MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou , China.
authors.forename: Da
authors.initials: D
authors.lastname: Xing
authors.affiliation: a MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou , China.|d Institute of Neuroscience, Suzhou University , Soochow , China.
authors.forename: Quan-Hong
authors.initials: QH
authors.lastname: Ma
authors.affiliation: b The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University , Kunming , China.|c Department of Anatomy and Developmental Biology , Monash University , Clayton , Melbourne , Australia.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D000071636:Protein Phosphatase 2C / Q000172:deficiency / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000071636:Protein Phosphatase 2C; D018091:Receptors, AMPA; C000607468:Ppm1d protein, mouse
keywords: CaMKII; GluR1; LTD; LTP; Wip1; hippocampus