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

Author:

Wu Yu12,Lv Xinyou12,Wang Haiting12,Qian Kai12,Ding Jinjun12,Wang Jiejie12,Hua Shushan12,Sun Tiancheng12,Zhou Yiting34,Yu Lina12,Qiu Shuang125ORCID

Affiliation:

1. Department of Neurobiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China

2. Department of Anesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China

3. Department of Biochemistry, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China

4. Department of Orthopaedic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China

5. NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310058, China

Abstract

Abstract 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 α1 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 APPL1-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Zhejiang Province for Distinguished Young Scholars

Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences

Fundamental Research Funds for the Central Universities of China

Chinese Ministry of Education Project 111 Program

Key Realm R&D Program of Guangdong Province

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Genetics,Molecular Biology,General Medicine

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