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Wip1 phosphatase positively modulates dendritic spine morphology and memory processes through the p38MAPK signaling pathway
Fernandez, Francesca Soon, Irene Li, Zeng Kuan, Tan Chee Min, Deng Hong Wong, Esther Sook-Miin Demidov, Oleg N. Paterson, Malcom C. Dawe, Gavin Bulavin, Dmitry V.
Fernandez, Francesca
Soon, Irene
Li, Zeng
Kuan, Tan Chee
Min, Deng Hong
Wong, Esther Sook-Miin
Demidov, Oleg N.
Paterson, Malcom C.
Dawe, Gavin
Bulavin, Dmitry V.
Abstract
Dendritic spine morphology is modulated by protein kinase p38, a mitogen-activated protein (MAPK), in the hippocampus. Protein p38MAPK is a substrate of wip1, a protein phosphatase. The role of wip1 in the central nervous system (CNS) has never been explored. Here, we report a novel function of wip1 in dendritic spine morphology and memory processes. Wip1 deficiency decreases dendritic spine size and density in pyramidal neurons of the hippocampal CA1 region. Simultaneously, impairments in object recognition tasks and contextual memory occur in wip1 deficient mice, but are reversed in wip1/p38 double mutant mice. Thus, our findings demonstrate that wip1 modulates dendritic morphology and memory processes through the p38MAPK signaling pathway. In addition to the well-characterized role of the wip1/p38MAPK in cell death and differentiation, we revealed the novel contribution of wip1 to cognition and dendritic spine morphology, which may suggest new approaches to treating neurodegenerative disorders.
Keywords
Wip1 phosphatase, p38MAPK, memory, dendritic spine morphology, hippocampus, signaling pathway
Date
2012
Type
Journal article
Journal
Cell Adhesion and Migration
Book
Volume
6
Issue
4
Page Range
333-343
Article Number
ACU Department
School of Behavioural and Health Sciences
Faculty of Health Sciences
Faculty of Health Sciences
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled