RRC ID 35794
著者 Kusakari S, Saitow F, Ago Y, Shibasaki K, Sato-Hashimoto M, Matsuzaki Y, Kotani T, Murata Y, Hirai H, Matsuda T, Suzuki H, Matozaki T, Ohnishi H.
タイトル Shp2 in forebrain neurons regulates synaptic plasticity, locomotion, and memory formation in mice.
ジャーナル Mol Cell Biol
Abstract Shp2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) regulates neural cell differentiation. It is also expressed in postmitotic neurons, however, and mutations of Shp2 are associated with clinical syndromes characterized by mental retardation. Here we show that conditional-knockout (cKO) mice lacking Shp2 specifically in postmitotic forebrain neurons manifest abnormal behavior, including hyperactivity. Novelty-induced expression of immediate-early genes and activation of extracellular-signal-regulated kinase (Erk) were attenuated in the cerebral cortex and hippocampus of Shp2 cKO mice, suggestive of reduced neuronal activity. In contrast, ablation of Shp2 enhanced high-K(+)-induced Erk activation in both cultured cortical neurons and synaptosomes, whereas it inhibited that induced by brain-derived growth factor in cultured neurons. Posttetanic potentiation and paired-pulse facilitation were attenuated and enhanced, respectively, in hippocampal slices from Shp2 cKO mice. The mutant mice also manifested transient impairment of memory formation in the Morris water maze. Our data suggest that Shp2 contributes to regulation of Erk activation and synaptic plasticity in postmitotic forebrain neurons and thereby controls locomotor activity and memory formation.
巻・号 35(9)
ページ 1557-72
公開日 2015-5-1
DOI 10.1128/MCB.01339-14
PII MCB.01339-14
PMID 25713104
PMC PMC4387209
MeSH Animals Behavior, Animal Cells, Cultured Gene Expression Regulation Genes, Immediate-Early Locomotion* MAP Kinase Signaling System Male Memory* Mice / genetics Mice / physiology* Mice, Knockout Neuronal Plasticity* Neurons / cytology Neurons / metabolism Prosencephalon / cytology* Prosencephalon / physiology Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics* Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism RNA Interference RNA, Small Interfering / genetics
IF 3.611
引用数 19
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
遺伝子材料 CS-CDF-EG-PRE-RfA (RDB07722) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).