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Updated: Jun 28, 2026
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A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
AMPA receptor trafficking and synaptic plasticity require SQSTM1/p62
Jianxiong Jiang1, Kodeeswaran Parameshwaran, M Lamar Seibenhener
1Department of Biological Sciences and Program in Cellular and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA.
Hippocampus
|November 13, 2008
Summary
The protein p62 interacts with AMPA receptors, regulating their surface delivery and synaptic plasticity. Mice lacking p62 show impaired hippocampal long-term potentiation, highlighting p62
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- SQSTM1/p62 acts as a scaffold for atypical protein kinase Cs (aPKC).
- PKC-mediated phosphorylation of AMPA receptors influences their postsynaptic membrane insertion.
Purpose of the Study:
- To investigate the interaction between p62 and AMPA receptor subunits.
- To determine p62's role in AMPA receptor trafficking and phosphorylation.
Main Methods:
- Co-immunoprecipitation assays to test protein interactions.
- Western blotting to assess protein phosphorylation.
- Electrophysiological recordings in mouse models to evaluate synaptic plasticity.
Main Results:
- p62 directly interacts with the GluR1 receptor's intracellular loop L2-3 via its ZZ-type zinc finger domain.
- p62 and aPKC phosphorylation are essential for surface delivery of AMPA receptors.
- p62-deficient mice exhibit impaired hippocampal CA1 long-term potentiation (LTP), reduced GluR1 surface expression, and decreased S818 phosphorylation.
- A conserved ISExSL motif was identified in p62-interacting aPKC substrates.
Conclusions:
- p62 is the first identified protein to interact with a region of the GluR receptor outside the C-terminal tail.
- p62 and aPKC-mediated phosphorylation cooperate to regulate AMPA receptor trafficking.
- This interaction is crucial for hippocampal synaptic plasticity and LTP.
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