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

ABSTRACT: 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

SUBMITTER: Wang G 

PROVIDER: S-EPMC5584878 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature