Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation
Copyright policy )Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation
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.
- Johns Hopkins University School of Medicine United States
- Massachusetts Institute of Technology United States
- Johns Hopkins Medicine United States
- Johns Hopkins University Sch of Medicine United States
- John Hopkins University School of Medecine United States
Neurons, Lipoylation, Cell Membrane, Long-Term Potentiation, Neuropeptides, Video Recording, Membrane Proteins, In Vitro Techniques, Hippocampus, Article, Rats, Mice, Inbred C57BL, Cytoskeletal Proteins, Mice, Microscopy, Fluorescence, Mutation, Animals, Receptors, AMPA, Phosphorylation, Cells, Cultured, Protein Kinase C
Neurons, Lipoylation, Cell Membrane, Long-Term Potentiation, Neuropeptides, Video Recording, Membrane Proteins, In Vitro Techniques, Hippocampus, Article, Rats, Mice, Inbred C57BL, Cytoskeletal Proteins, Mice, Microscopy, Fluorescence, Mutation, Animals, Receptors, AMPA, Phosphorylation, Cells, Cultured, Protein Kinase C
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