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

Authors: Wang, Guan  Li, Shaomin  Gilbert, James  Gritton, Howard J  Wang, Zemin  Li, Zhangyuan  Han, Xue  Selkoe, Dennis J  Man, Heng-Ye 
Citation: Wang G, etal., Cell Rep. 2017 Aug 8;20(6):1335-1347. doi: 10.1016/j.celrep.2017.07.030.
Pubmed: (View Article at PubMed) PMID:28793258
DOI: Full-text: DOI:10.1016/j.celrep.2017.07.030

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.

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CRRD Object Information
CRRD ID: 13702139
Created: 2018-07-18
Species: All species
Last Modified: 2018-07-18
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.