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Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development
文献类型：期刊论文
| 作者 | Zhu, YC ; Li, D ; Wang, L ; Lu, B ; Zheng, J ; Zhao, SL ; Zeng, R ; Xiong, ZQ |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2013 |
| 卷号 | 110期号:22页码:9118-9123 |
| 关键词 | DENSITY PROTEIN PSD-95 POSTSYNAPTIC DENSITY NEURONAL DEVELOPMENT RETT-SYNDROME INFANTILE SPASMS PLASTICITY KINASES GENE LOCALIZATION RETARDATION |
| ISSN号 | 0027-8424 |
| 通讯作者 | Xiong, ZQ (reprint author), Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China.,xiongzhiqi@ion.ac.cn |
| 英文摘要 | The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5-PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation- dependent CDKL5-PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutationsmay be implicated in the pathogenesis of CDKL5-related disorders. |
| 学科主题 | Science & Technology - Other Topics |
| 收录类别 | SCI |
| 资助信息 | 973 Program [2011CBA00400]; National Natural Science Foundation of China [30925016, 31021063, 31123002]; Program of Shanghai Subject Chief Scientist Grant [12XD1405500] |
| 语种 | 英语 |
| WOS记录号 | WOS:000320500000084 |
| 公开日期 | 2013-11-06 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/2573]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Zhu, YC,Li, D,Wang, L,et al. Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2013,110(22):9118-9123. |
| APA | Zhu, YC.,Li, D.,Wang, L.,Lu, B.,Zheng, J.,...&Xiong, ZQ.(2013).Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,110(22),9118-9123. |
| MLA | Zhu, YC,et al."Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 110.22(2013):9118-9123. |
入库方式： OAI收割
来源：上海神经科学研究所
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