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...
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| Formato: | Artigo |
| Idioma: | en_US |
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Nature Publishing Group
2010
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| Acesso em linha: | http://hdl.handle.net/1721.1/52604 https://orcid.org/0000-0002-3854-5968 |
| _version_ | 1826217370240155648 |
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| author | Lin, Da-Ting Makino, Yuichi Sharma, Kamal Hayashi, Takashi Neve, Rachael L. Takamiya, Kogo Huganir, Richard L. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Lin, Da-Ting Makino, Yuichi Sharma, Kamal Hayashi, Takashi Neve, Rachael L. Takamiya, Kogo Huganir, Richard L. |
| author_sort | Lin, Da-Ting |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:02:35Z |
| format | Article |
| id | mit-1721.1/52604 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:02:35Z |
| publishDate | 2010 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/526042022-09-29T23:16:05Z Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation Lin, Da-Ting Makino, Yuichi Sharma, Kamal Hayashi, Takashi Neve, Rachael L. Takamiya, Kogo Huganir, Richard L. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Neve, Rachael L. Neve, Rachael L. 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. 2010-03-15T20:47:06Z 2010-03-15T20:47:06Z 2009-06 2009-03 Article http://purl.org/eprint/type/SubmittedJournalArticle 1097-6256 http://hdl.handle.net/1721.1/52604 Lin, Da-Ting, et al. "Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation." (2009) Nature Neuroscience 12, 879 - 887 https://orcid.org/0000-0002-3854-5968 en_US http://dx.doi.org/10.1038/nn.2351 Nature Neuroscience 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. application/pdf Nature Publishing Group Rachael Neve |
| spellingShingle | Lin, Da-Ting Makino, Yuichi Sharma, Kamal Hayashi, Takashi Neve, Rachael L. Takamiya, Kogo Huganir, Richard L. Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation |
| title | Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation |
| title_full | Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation |
| title_fullStr | Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation |
| title_full_unstemmed | Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation |
| title_short | Regulation of AMPA receptor extrasynaptic insertion by 4.1N, phosphorylation and palmitoylation |
| title_sort | regulation of ampa receptor extrasynaptic insertion by 4 1n phosphorylation and palmitoylation |
| url | http://hdl.handle.net/1721.1/52604 https://orcid.org/0000-0002-3854-5968 |
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