title: Wip1 phosphatase positively modulates dendritic spine morphology and memory processes through the p38MAPK signaling pathway.
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.
authors.affiliation: Institute of Molecular and Cell Biology, Proteos, Singapore.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fernandez
authors.forename: Irene
authors.initials: I
authors.lastname: Soon
authors.forename: Zeng
authors.initials: Z
authors.lastname: Li
authors.forename: Tan Chee
authors.initials: TC
authors.lastname: Kuan
authors.forename: Deng Hong
authors.initials: DH
authors.lastname: Min
authors.forename: Esther Sook-Miin
authors.initials: ES
authors.lastname: Wong
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Demidov
authors.forename: Malcom C
authors.initials: MC
authors.lastname: Paterson
authors.forename: Gavin
authors.initials: G
authors.lastname: Dawe
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Bulavin
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D048430:Cell Shape; D002478:Cells, Cultured; D003213:Conditioning, Psychological; D049229:Dendritic Spines / Q000201:enzymology* / Q000502:physiology; D005239:Fear; D005556:Form Perception; D046352:Freezing Reaction, Cataleptic; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D020935:MAP Kinase Signaling System; D018782:Maze Learning; D008568:Memory; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010749:Phosphoprotein Phosphatases / Q000172:deficiency* / Q000235:genetics; D000071636:Protein Phosphatase 2C; D017966:Pyramidal Cells / Q000201:enzymology / Q000648:ultrastructure; D048051:p38 Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C