The kinase activity of EphA4 mediates homeostatic scaling-down of synaptic strength via activation of Cdk5
文献类型：期刊论文
| 作者 | Peng, YR ; Hou, ZH ; Yu, X |
| 刊名 | NEUROPHARMACOLOGY
 |
| 出版日期 | 2013 |
| 卷号 | 65页码:232-243 |
| ISSN号 | 0028-3908 |
| 关键词 | DENDRITIC SPINE MORPHOLOGY NEURAL DEVELOPMENT NERVOUS-SYSTEM NEUROTRANSMITTER RELEASE HEBBS POSTULATE AMPA RECEPTOR PLASTICITY EXPRESSION EPHRINS POLO-LIKE-KINASE-2 |
| 通讯作者 | Yu, X (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,yuxiang@ion.ac.cn |
| 英文摘要 | Neurons within a network have the ability to homeostatically scale-down their excitatory synaptic strength under conditions of persistent neuronal activity elevation, a process pivotal to neural circuit stability. How this homeostatic regulation is achieved at the molecular level in developing neural circuits, which face gradually elevated neuronal activity as part of circuit wiring, is not well-understood. Using dissociated hippocampal neuronal cultures, we identified a critical and cell autonomous role for the receptor tyrosine kinase EphA4 in mediating activity-induced homeostatic down-regulation of excitatory synaptic strength. Reducing the endogenous level of EphA4 in individual neurons by RNAi effectively blocked activity-induced scaling-down of excitatory synaptic strength, while co-transfection of RNAi resistant EphA4 rescued this effect. Furthermore, interfering with EphA4 forward signaling using EphA4-Fc blocked activity-induced homeostatic synaptic scaling-down, while direct activation of EphA4 with its ligand EphrinA1 weakened excitatory synaptic strength. Up- or down-regulating EphA4 function in individual neurons also did not affect the density of excitatory synapses. The kinase activities of EphA4 and its downstream effector Cdk5 were both required for homeostatic synaptic scaling, as overexpression of EphA4 with constitutively active kinase activity reduced excitatory synaptic strength, while interfering with either the kinase activity of EphA4 or Cdk5 blocked activity-induced synaptic scaling. Consistently, the activities of EphA4 and Cdk5 increased significantly during global and persistent activity elevation. Together, our work demonstrated that the kinase activity of EphA4, via activation of downstream Cdk5 activity, mediates the scaling-down. of excitatory synaptic strength under conditions of global activity elevation. (C) 2012 Elsevier Ltd. All rights reserved. |
| 学科主题 | Neurosciences & Neurology ; Pharmacology & Pharmacy |
| 资助信息 | Ministry of Science and Technology [2011CBA00400]; National Natural Science Foundation of China [31125015, 31021063] |
| 收录类别 | SCI |
| 语种 | 英语 |
| 公开日期 | 2013-06-04 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/2530]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Peng, YR,Hou, ZH,Yu, X. The kinase activity of EphA4 mediates homeostatic scaling-down of synaptic strength via activation of Cdk5[J]. NEUROPHARMACOLOGY,2013,65:232-243. |
| APA | Peng, YR,Hou, ZH,&Yu, X.(2013).The kinase activity of EphA4 mediates homeostatic scaling-down of synaptic strength via activation of Cdk5.NEUROPHARMACOLOGY,65,232-243. |
| MLA | Peng, YR,et al."The kinase activity of EphA4 mediates homeostatic scaling-down of synaptic strength via activation of Cdk5".NEUROPHARMACOLOGY 65(2013):232-243. |
入库方式： OAI收割
来源：上海神经科学研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。