文献类型：期刊文献

英文题名：Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development

作者：Zhu, Yong-Chuan[1,2];Li, Dan[1,2];Wang, Lu[1,2];Lu, Bin[1,2];Zheng, Jing[4];Zhao, Shi-Lin[3];Zeng, Rong[3];Xiong, Zhi-Qi[1,2]

机构：[1]Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China;[2]Chinese Acad Sci, State Key Lab Neurosci, Shanghai 200031, Peoples R China;[3]Chinese Acad Sci, Key Lab Syst Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China;[4]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2013

卷号：110

期号：22

起止页码：9118

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000320500000084)】；

基金：We thank Dr. Qian Hu for assistance with confocal imaging and Yang Li for help with the in utero electroporation experiments. This work was supported by 973 Program Grant 2011CBA00400; National Natural Science Foundation of China Grants 30925016, 31021063, and 31123002; and Program of Shanghai Subject Chief Scientist Grant 12XD1405500.

语种：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.