Distinct structural pathways coordinate the activiation 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...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2016
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| _version_ | 1797091156337623040 |
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| author | Dawe, G Musgaard, M Biggin, P al., E |
| author_facet | Dawe, G Musgaard, M Biggin, P al., E |
| author_sort | Dawe, G |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T03:28:59Z |
| format | Journal article |
| id | oxford-uuid:ba08d104-aa6d-4099-8fb9-108ee7369f51 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:28:59Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:ba08d104-aa6d-4099-8fb9-108ee7369f512022-03-27T05:07:09ZDistinct structural pathways coordinate the activiation of AMPA receptor-auxiliary subunit complexesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ba08d104-aa6d-4099-8fb9-108ee7369f51EnglishSymplectic Elements at OxfordElsevier2016Dawe, GMusgaard, MBiggin, Pal., ENeurotransmitter-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. |
| spellingShingle | Dawe, G Musgaard, M Biggin, P al., E Distinct structural pathways coordinate the activiation of AMPA receptor-auxiliary subunit complexes |
| title | Distinct structural pathways coordinate the activiation of AMPA receptor-auxiliary subunit complexes |
| title_full | Distinct structural pathways coordinate the activiation of AMPA receptor-auxiliary subunit complexes |
| title_fullStr | Distinct structural pathways coordinate the activiation of AMPA receptor-auxiliary subunit complexes |
| title_full_unstemmed | Distinct structural pathways coordinate the activiation of AMPA receptor-auxiliary subunit complexes |
| title_short | Distinct structural pathways coordinate the activiation of AMPA receptor-auxiliary subunit complexes |
| title_sort | distinct structural pathways coordinate the activiation of ampa receptor auxiliary subunit complexes |
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