Article abstract
Nature Neuroscience 12, 879 - 887 (2009)
Published online: 7 June 2009 | Corrected online: 14 June 2009 | doi:10.1038/nn.2351
Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation
Da-Ting Lin1, Yuichi Makino1, Kamal Sharma1, Takashi Hayashi1, Rachael Neve2, Kogo Takamiya1,3 & Richard L Huganir1
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.
- Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
- Massachusetts Institute of Technology, The Picower Institute, Cambridge, Massachusetts, USA.
- Present address: Department of Integrative Physiology, University of Miyazaki Faculty of Medicine, Miyazaki, Japan.
Correspondence to: Richard L Huganir1 e-mail: rhuganir@jhmi.edu
M), 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX, 20 mM) and DL(–)-2-amino-5-phosphonovaleric acid (AP5, 200 M) substantially the insertion frequency of R1pH (Fig. 2b)" should read "Acute suppression of excitatory neuronal activity by applying a cocktail of tetrodotoxin (TTX, 1 M), 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX, 20 M) and DL(–)-2-amino-5-phosphonovaleric acid (AP5, 200 M) substantially reduced the insertion frequency of R1pH (Fig. 2b)." In the last paragraph of the fourth section under Results, the sentence "Following PKC activation, we detected greater phosphorylation of S818 in GluR1C811S compared with of GluR1 (Fig. 6e,f)" should read "Following PKC activation, we detected greater phosphorylation of S818 in GluR1C811S compared with that of GluR1 (Fig. 6e,f)." These errors have been corrected for the print, PDF and HTML versions of this article.MORE ARTICLES LIKE THIS
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