期刊论文详细信息
Cell Reports
Crucial Roles for SIRT2 and AMPA Receptor Acetylation in Synaptic Plasticity and Memory
Shaomin Li1  Zhangyuan Li1  Dennis J. Selkoe1  Zemin Wang1  Guan Wang2  James Gilbert2  Heng-Ye Man2  Howard J. Gritton3  Xue Han3 
[1] Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA;Department of Biology, Boston University, Boston, MA 02215, USA;Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA;
关键词: AMPA receptors;    AMPARs;    receptor trafficking;    sirtuin 2;    deacetylase;    acetylation;    ubiquitination;    synaptic plasticity;    learning and memory;    cognitive function;   
DOI  :  10.1016/j.celrep.2017.07.030
来源: DOAJ
【 摘 要 】

AMPA receptors (AMPARs) mediate fast excitatory synaptic transmission and are crucial for synaptic plasticity, learning, and memory. However, the molecular control of AMPAR stability and its neurophysiological significance remain unclear. Here, we report that AMPARs are subject to lysine acetylation at their C termini. Acetylation reduces AMPAR internalization and degradation, leading to increased cell-surface localization and prolonged receptor half-life. Through competition for the same lysine residues, acetylation intensity is inversely related to the levels of AMPAR ubiquitination. We find that sirtuin 2 (SIRT2) acts as an AMPAR deacetylase regulating AMPAR trafficking and proteostasis. SIRT2 knockout mice (Sirt2−/−) show marked upregulation in AMPAR acetylation and protein accumulation. Both Sirt2−/− mice and mice expressing acetylation mimetic GluA1 show aberrant synaptic plasticity, accompanied by impaired learning and memory. These findings establish SIRT2-regulated lysine acetylation as a form of AMPAR post-translational modification that regulates its turnover, as well as synaptic plasticity and cognitive function.

【 授权许可】

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