Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons

作     者：Yu Wu Xinyou Lv Haiting Wang Kai Qian Jinjun Ding Jiejie Wang Shushan Hua Tiancheng Sun Yiting Zhou Lina Yu Shuang Qiu Yu Wu;Xinyou Lv;Haiting Wang;Kai Qian;Jinjun Ding;Jiejie Wang;Shushan Hua;Tiancheng Sun;Yiting Zhou;Lina Yu;Shuang Qiu

作者机构：Department of NeurobiologySecond Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Department of AnesthesiologySecond Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Department of BiochemistrySecond Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Department of Orthopaedic SurgerySecond Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China NHC and CAMS Key Laboratory of Medical NeurobiologyMOE Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2021年第13卷第5期

页      面：335-346页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学] 

基　　金：This work was supported by the National Natural Science Foundation of China(81671049 and 91732102 to S.Q 31900722 to Y.W.) Natural Science Foundation of Zhejiang Province for Distinguished Young Scholars(LR16C090001 to S.Q.) Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT31041) Fundamental Research Funds for the Central Universities of China(2019XZZX001-01-1A to S.Q.) the Chinese Ministry of Education Project 111 Program(B13026 to S.Q.) Key Realm R&D Program of Guangdong Province(2019B030335001) 

主　　题：APPL1 excitation-transcription coupling synaptic plasticity chromatin remodeling gene transcription 

摘      要：Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses,and thereby translate information about the external environment into internal neuronal *** retrograde signaling is critical to dendritic growth,synapse development,and neuronal ***,we demonstrate that neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor *** the interaction of APPL1 with Importin ocl abolishes nuclear accumulation of APPL1,which in turn decreases the levels of histone *** further demonstrate that retrograde translocation of APPL1 is required for the regulation of gene transcription and then maintenance of hippocampal late-phase long-term ***,these results illustrate an APPLl-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.