A network of autism linked genes stabilizes two pools of synaptic GABAA receptors
Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABAA receptors are stabili...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2015-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/09648 |
| _version_ | 1811201087478169600 |
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| author | Xia-Jing Tong Zhitao Hu Yu Liu Dorian Anderson Joshua M Kaplan |
| author_facet | Xia-Jing Tong Zhitao Hu Yu Liu Dorian Anderson Joshua M Kaplan |
| author_sort | Xia-Jing Tong |
| collection | DOAJ |
| description | Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABAA receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABAA receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABAA receptors are stabilized by the synaptic adhesion molecules Neurexin and Neuroligin. Inhibitory post-synaptic currents are eliminated in double mutants lacking both scaffolds. Neurexin, Neuroligin, and CASK mutations are all linked to Autism Spectrum Disorders (ASD). Our results suggest that these mutations may directly alter inhibitory transmission, which could contribute to the developmental and cognitive deficits observed in ASD. |
| first_indexed | 2024-04-12T02:14:59Z |
| format | Article |
| id | doaj.art-c57c1175c2f24393b3d3c20a22785238 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:14:59Z |
| publishDate | 2015-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c57c1175c2f24393b3d3c20a227852382022-12-22T03:52:17ZengeLife Sciences Publications LtdeLife2050-084X2015-11-01410.7554/eLife.09648A network of autism linked genes stabilizes two pools of synaptic GABAA receptorsXia-Jing Tong0Zhitao Hu1Yu Liu2Dorian Anderson3Joshua M Kaplan4Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States; Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States; Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States; Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States; Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States; Department of Neurobiology, Harvard Medical School, Boston, United StatesChanging receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABAA receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABAA receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABAA receptors are stabilized by the synaptic adhesion molecules Neurexin and Neuroligin. Inhibitory post-synaptic currents are eliminated in double mutants lacking both scaffolds. Neurexin, Neuroligin, and CASK mutations are all linked to Autism Spectrum Disorders (ASD). Our results suggest that these mutations may directly alter inhibitory transmission, which could contribute to the developmental and cognitive deficits observed in ASD.https://elifesciences.org/articles/09648autismsynaptic transmissionGABA-A receptorsCASKneurexinneuroligin |
| spellingShingle | Xia-Jing Tong Zhitao Hu Yu Liu Dorian Anderson Joshua M Kaplan A network of autism linked genes stabilizes two pools of synaptic GABAA receptors eLife autism synaptic transmission GABA-A receptors CASK neurexin neuroligin |
| title | A network of autism linked genes stabilizes two pools of synaptic GABAA receptors |
| title_full | A network of autism linked genes stabilizes two pools of synaptic GABAA receptors |
| title_fullStr | A network of autism linked genes stabilizes two pools of synaptic GABAA receptors |
| title_full_unstemmed | A network of autism linked genes stabilizes two pools of synaptic GABAA receptors |
| title_short | A network of autism linked genes stabilizes two pools of synaptic GABAA receptors |
| title_sort | network of autism linked genes stabilizes two pools of synaptic gabaa receptors |
| topic | autism synaptic transmission GABA-A receptors CASK neurexin neuroligin |
| url | https://elifesciences.org/articles/09648 |
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