Crucial Roles for SIRT2 and AMPA Receptor Acetylation in Synaptic Plasticity and Memory

Guan Wang, Shaomin Li, James Gilbert, Howard J. Gritton, Zemin Wang, Zhangyuan Li, Xue Han, Dennis J. Selkoe, Heng Ye Man

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1335-1347
Number of pages13
JournalCell Reports
Issue number6
StatePublished - Aug 8 2017
Externally publishedYes


  • acetylation
  • AMPA receptors
  • AMPARs
  • cognitive function
  • deacetylase
  • learning and memory
  • receptor trafficking
  • sirtuin 2
  • synaptic plasticity
  • ubiquitination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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