Functional assessment of the NMDA receptor variant GluN2AR586K [version 1; referees: 1 approved, 2 approved with reservations]
Background: The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor that has important roles in synaptogenesis, synaptic transmission, and synaptic plasticity. Recently, a large number of rare genetic variants have been found in NMDAR subunits in people with neurodevelopmental...
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| Format: | Article |
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Wellcome
2017-03-01
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| Series: | Wellcome Open Research |
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| Online Access: | https://wellcomeopenresearch.org/articles/2-20/v1 |
| _version_ | 1818571913144827904 |
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| author | Katie F.M. Marwick Peter Parker Paul Skehel Giles Hardingham David J.A. Wyllie |
| author_facet | Katie F.M. Marwick Peter Parker Paul Skehel Giles Hardingham David J.A. Wyllie |
| author_sort | Katie F.M. Marwick |
| collection | DOAJ |
| description | Background: The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor that has important roles in synaptogenesis, synaptic transmission, and synaptic plasticity. Recently, a large number of rare genetic variants have been found in NMDAR subunits in people with neurodevelopmental disorders, and also in healthy individuals. One such is the GluN2AR586K variant, found in a person with intellectual disability. Identifying the functional consequences, if any, of such variants allows their potential contribution to pathogenesis to be assessed. Here, we assessed the effect of the GluN2AR586K variant on NMDAR pore properties. Methods: We expressed recombinant NMDARs with and without the GluN2AR586K variant in Xenopus laevis oocytes and in primary cultured mouse neurons, and made electrophysiological recordings assessing Mg2+ block, single-channel conductance, mean open time and current density. Results: The GluN2AR586K variant was not found to influence any of the properties assessed. Conclusions: Our findings suggest it is unlikely that the GluN2AR586K variant contributes to the pathogenesis of neurodevelopmental disorder. |
| first_indexed | 2024-12-14T18:50:31Z |
| format | Article |
| id | doaj.art-e5d9b0fe164f473a8e17e9b6cf1392f2 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-14T18:50:31Z |
| publishDate | 2017-03-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-e5d9b0fe164f473a8e17e9b6cf1392f22022-12-21T22:51:16ZengWellcomeWellcome Open Research2398-502X2017-03-01210.12688/wellcomeopenres.10985.111843Functional assessment of the NMDA receptor variant GluN2AR586K [version 1; referees: 1 approved, 2 approved with reservations]Katie F.M. Marwick0Peter Parker1Paul Skehel2Giles Hardingham3David J.A. Wyllie4Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UKCentre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UKCentre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UKCentre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UKCentre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UKBackground: The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor that has important roles in synaptogenesis, synaptic transmission, and synaptic plasticity. Recently, a large number of rare genetic variants have been found in NMDAR subunits in people with neurodevelopmental disorders, and also in healthy individuals. One such is the GluN2AR586K variant, found in a person with intellectual disability. Identifying the functional consequences, if any, of such variants allows their potential contribution to pathogenesis to be assessed. Here, we assessed the effect of the GluN2AR586K variant on NMDAR pore properties. Methods: We expressed recombinant NMDARs with and without the GluN2AR586K variant in Xenopus laevis oocytes and in primary cultured mouse neurons, and made electrophysiological recordings assessing Mg2+ block, single-channel conductance, mean open time and current density. Results: The GluN2AR586K variant was not found to influence any of the properties assessed. Conclusions: Our findings suggest it is unlikely that the GluN2AR586K variant contributes to the pathogenesis of neurodevelopmental disorder.https://wellcomeopenresearch.org/articles/2-20/v1Developmental & Pediatric NeurologyMedical Genetics |
| spellingShingle | Katie F.M. Marwick Peter Parker Paul Skehel Giles Hardingham David J.A. Wyllie Functional assessment of the NMDA receptor variant GluN2AR586K [version 1; referees: 1 approved, 2 approved with reservations] Wellcome Open Research Developmental & Pediatric Neurology Medical Genetics |
| title | Functional assessment of the NMDA receptor variant GluN2AR586K [version 1; referees: 1 approved, 2 approved with reservations] |
| title_full | Functional assessment of the NMDA receptor variant GluN2AR586K [version 1; referees: 1 approved, 2 approved with reservations] |
| title_fullStr | Functional assessment of the NMDA receptor variant GluN2AR586K [version 1; referees: 1 approved, 2 approved with reservations] |
| title_full_unstemmed | Functional assessment of the NMDA receptor variant GluN2AR586K [version 1; referees: 1 approved, 2 approved with reservations] |
| title_short | Functional assessment of the NMDA receptor variant GluN2AR586K [version 1; referees: 1 approved, 2 approved with reservations] |
| title_sort | functional assessment of the nmda receptor variant glun2ar586k version 1 referees 1 approved 2 approved with reservations |
| topic | Developmental & Pediatric Neurology Medical Genetics |
| url | https://wellcomeopenresearch.org/articles/2-20/v1 |
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