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Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes
Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a commo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819453/ https://www.ncbi.nlm.nih.gov/pubmed/26924438 http://dx.doi.org/10.1016/j.neuron.2016.01.038 |
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author | Dawe, G. Brent Musgaard, Maria Aurousseau, Mark R.P. Nayeem, Naushaba Green, Tim Biggin, Philip C. Bowie, Derek |
author_facet | Dawe, G. Brent Musgaard, Maria Aurousseau, Mark R.P. Nayeem, Naushaba Green, Tim Biggin, Philip C. Bowie, Derek |
author_sort | Dawe, G. Brent |
collection | PubMed |
description | Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits. |
format | Online Article Text |
id | pubmed-4819453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48194532016-04-14 Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes Dawe, G. Brent Musgaard, Maria Aurousseau, Mark R.P. Nayeem, Naushaba Green, Tim Biggin, Philip C. Bowie, Derek Neuron Article Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits. Cell Press 2016-03-16 /pmc/articles/PMC4819453/ /pubmed/26924438 http://dx.doi.org/10.1016/j.neuron.2016.01.038 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dawe, G. Brent Musgaard, Maria Aurousseau, Mark R.P. Nayeem, Naushaba Green, Tim Biggin, Philip C. Bowie, Derek Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes |
title | Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes |
title_full | Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes |
title_fullStr | Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes |
title_full_unstemmed | Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes |
title_short | Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes |
title_sort | distinct structural pathways coordinate the activation of ampa receptor-auxiliary subunit complexes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819453/ https://www.ncbi.nlm.nih.gov/pubmed/26924438 http://dx.doi.org/10.1016/j.neuron.2016.01.038 |
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