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 representations.This retrograde signaling is critical to dendritic growth,synapse development,and neuronal plasticity.Here,we demonstrate that neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor APPL1.Disrupting the interaction of APPL1 with Importin ocl abolishes nuclear accumulation of APPL1,which in turn decreases the levels of histone acetylation.We further demonstrate that retrograde translocation of APPL1 is required for the regulation of gene transcription and then maintenance of hippocampal late-phase long-term potentiation.Thus,these results illustrate an APPLl-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.
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).
