| RRC ID |
35794
|
| Author |
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.
|
| Title |
Shp2 in forebrain neurons regulates synaptic plasticity, locomotion, and memory formation in mice.
|
| Journal |
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.
|
| Volume |
35(9)
|
| Pages |
1557-72
|
| Published |
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
|
| Times Cited |
19
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| DNA material |
CS-CDF-EG-PRE-RfA (RDB07722)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394). |
