Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation
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Huganirregulationofampareceptor.pdf
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Author(s)
Lin, Da-Ting
Makino, Yuichi
Sharma, Kamal
Hayashi, Takashi
Neve, Rachael L.
Takamiya, Kogo
Huganir, Richard L.
Date Issued
June 2009
Journal
Nature Neuroscience
Publisher
Nature Publishing Group
Citation
Lin, Da-Ting, et al. "Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation." (2009) Nature Neuroscience 12, 879 - 887
Version
Author's final manuscript
Abstract
The insertion of AMPA receptors (AMPARs) into the plasma membrane is an important step in the synaptic delivery of AMPARs during the expression of synaptic plasticity. However, the molecular mechanisms regulating AMPAR insertion remain elusive. By directly visualizing individual insertion events of the AMPAR subunit GluR1 in rodents, we found that the protein 4.1N was required for activity-dependent GluR1 insertion. Protein kinase C (PKC) phosphorylation of the serine 816 (S816) and S818 residues of GluR1 enhanced 4.1N binding to GluR1 and facilitated GluR1 insertion. In addition, palmitoylation of GluR1 C811 residue modulated PKC phosphorylation and GluR1 insertion. Finally, disrupting 4.1N-dependent GluR1 insertion decreased surface expression of GluR1 and the expression of long-term potentiation. Our study uncovers a previously unknown mechanism that governs activity-dependent GluR1 trafficking, reveals an interaction between AMPAR palmitoylation and phosphorylation, and underscores the functional importance of 4.1N in AMPAR trafficking and synaptic plasticity.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1038/nn.2351
