Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain
AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and are selectively recruited during activity-dependent plasticity to increase synaptic strength. A prerequisite for faithful signal transmission is the positioning and clustering of AMPARs at postsynaptic sites. The me...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/23024 |
| _version_ | 1811181445854527488 |
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| author | Jake F Watson Hinze Ho Ingo H Greger |
| author_facet | Jake F Watson Hinze Ho Ingo H Greger |
| author_sort | Jake F Watson |
| collection | DOAJ |
| description | AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and are selectively recruited during activity-dependent plasticity to increase synaptic strength. A prerequisite for faithful signal transmission is the positioning and clustering of AMPARs at postsynaptic sites. The mechanisms underlying this positioning have largely been ascribed to the receptor cytoplasmic C-termini and to AMPAR-associated auxiliary subunits, both interacting with the postsynaptic scaffold. Here, using mouse organotypic hippocampal slices, we show that the extracellular AMPAR N-terminal domain (NTD), which projects midway into the synaptic cleft, plays a fundamental role in this process. This highly sequence-diverse domain mediates synaptic anchoring in a subunit-selective manner. Receptors lacking the NTD exhibit increased mobility in synapses, depress synaptic transmission and are unable to sustain long-term potentiation (LTP). Thus, synaptic transmission and the expression of LTP are dependent upon an AMPAR anchoring mechanism that is driven by the NTD. |
| first_indexed | 2024-04-11T09:17:51Z |
| format | Article |
| id | doaj.art-2dad46a347e14213bc2600e64f1ef178 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:17:51Z |
| publishDate | 2017-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-2dad46a347e14213bc2600e64f1ef1782022-12-22T04:32:17ZengeLife Sciences Publications LtdeLife2050-084X2017-03-01610.7554/eLife.23024Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domainJake F Watson0https://orcid.org/0000-0002-8698-3823Hinze Ho1Ingo H Greger2https://orcid.org/0000-0002-7291-2581Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United KingdomNeurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United KingdomNeurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United KingdomAMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and are selectively recruited during activity-dependent plasticity to increase synaptic strength. A prerequisite for faithful signal transmission is the positioning and clustering of AMPARs at postsynaptic sites. The mechanisms underlying this positioning have largely been ascribed to the receptor cytoplasmic C-termini and to AMPAR-associated auxiliary subunits, both interacting with the postsynaptic scaffold. Here, using mouse organotypic hippocampal slices, we show that the extracellular AMPAR N-terminal domain (NTD), which projects midway into the synaptic cleft, plays a fundamental role in this process. This highly sequence-diverse domain mediates synaptic anchoring in a subunit-selective manner. Receptors lacking the NTD exhibit increased mobility in synapses, depress synaptic transmission and are unable to sustain long-term potentiation (LTP). Thus, synaptic transmission and the expression of LTP are dependent upon an AMPAR anchoring mechanism that is driven by the NTD.https://elifesciences.org/articles/23024AMPA receptorsynapseLTPN-terminal domainNTD |
| spellingShingle | Jake F Watson Hinze Ho Ingo H Greger Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain eLife AMPA receptor synapse LTP N-terminal domain NTD |
| title | Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain |
| title_full | Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain |
| title_fullStr | Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain |
| title_full_unstemmed | Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain |
| title_short | Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain |
| title_sort | synaptic transmission and plasticity require ampa receptor anchoring via its n terminal domain |
| topic | AMPA receptor synapse LTP N-terminal domain NTD |
| url | https://elifesciences.org/articles/23024 |
| work_keys_str_mv | AT jakefwatson synaptictransmissionandplasticityrequireampareceptoranchoringviaitsnterminaldomain AT hinzeho synaptictransmissionandplasticityrequireampareceptoranchoringviaitsnterminaldomain AT ingohgreger synaptictransmissionandplasticityrequireampareceptoranchoringviaitsnterminaldomain |