Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission
In the postsynaptic density of glutamatergic synapses, the discs large (DLG)-membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins coordinates a multiplicity of signaling pathways to maintain and regulate synaptic transmission. Postsynaptic density-93 (PSD-93) is the most varia...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Society for Neuroscience
2014
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| Online Access: | http://hdl.handle.net/1721.1/89137 https://orcid.org/0000-0001-7060-0288 https://orcid.org/0000-0003-0096-2288 |
| _version_ | 1826215138682732544 |
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| author | Kruger, Juliane M. Favaro, Plinio D. Liu, Mingna Kitlinska, Agata Huang, Xiaojie Raabe, Monika Akad, Derya S. Liu, Yanling Urlaub, Henning Dong, Yan Xu, Weifeng Schluter, Oliver M. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Kruger, Juliane M. Favaro, Plinio D. Liu, Mingna Kitlinska, Agata Huang, Xiaojie Raabe, Monika Akad, Derya S. Liu, Yanling Urlaub, Henning Dong, Yan Xu, Weifeng Schluter, Oliver M. |
| author_sort | Kruger, Juliane M. |
| collection | MIT |
| description | In the postsynaptic density of glutamatergic synapses, the discs large (DLG)-membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins coordinates a multiplicity of signaling pathways to maintain and regulate synaptic transmission. Postsynaptic density-93 (PSD-93) is the most variable paralog in this family; it exists in six different N-terminal isoforms. Probably because of the structural and functional variability of these isoforms, the synaptic role of PSD-93 remains controversial. To accurately characterize the synaptic role of PSD-93, we quantified the expression of all six isoforms in the mouse hippocampus and examined them individually in hippocampal synapses. Using molecular manipulations, including overexpression, gene knockdown, PSD-93 knock-out mice combined with biochemical assays, and slice electrophysiology both in rat and mice, we demonstrate that PSD-93 is required at different developmental synaptic states to maintain the strength of excitatory synaptic transmission. This strength is differentially regulated by the six isoforms of PSD-93, including regulations of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-active and inactive synapses, and activity-dependent modulations. Collectively, these results demonstrate that alternative combinations of N-terminal PSD-93 isoforms and DLG-MAGUK paralogs can fine-tune signaling scaffolds to adjust synaptic needs to regulate synaptic transmission. |
| first_indexed | 2024-09-23T16:17:10Z |
| format | Article |
| id | mit-1721.1/89137 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:17:10Z |
| publishDate | 2014 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/891372022-10-02T07:33:13Z Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission Kruger, Juliane M. Favaro, Plinio D. Liu, Mingna Kitlinska, Agata Huang, Xiaojie Raabe, Monika Akad, Derya S. Liu, Yanling Urlaub, Henning Dong, Yan Xu, Weifeng Schluter, Oliver M. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Liu, Mingna Xu, Weifeng In the postsynaptic density of glutamatergic synapses, the discs large (DLG)-membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins coordinates a multiplicity of signaling pathways to maintain and regulate synaptic transmission. Postsynaptic density-93 (PSD-93) is the most variable paralog in this family; it exists in six different N-terminal isoforms. Probably because of the structural and functional variability of these isoforms, the synaptic role of PSD-93 remains controversial. To accurately characterize the synaptic role of PSD-93, we quantified the expression of all six isoforms in the mouse hippocampus and examined them individually in hippocampal synapses. Using molecular manipulations, including overexpression, gene knockdown, PSD-93 knock-out mice combined with biochemical assays, and slice electrophysiology both in rat and mice, we demonstrate that PSD-93 is required at different developmental synaptic states to maintain the strength of excitatory synaptic transmission. This strength is differentially regulated by the six isoforms of PSD-93, including regulations of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-active and inactive synapses, and activity-dependent modulations. Collectively, these results demonstrate that alternative combinations of N-terminal PSD-93 isoforms and DLG-MAGUK paralogs can fine-tune signaling scaffolds to adjust synaptic needs to regulate synaptic transmission. National Institute of Mental Health (U.S.) (MH080310) 2014-09-02T18:10:09Z 2014-09-02T18:10:09Z 2013-09 2013-08 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/89137 Kruger, J. M., P. D. Favaro, M. Liu, A. Kitlinska, X. Huang, M. Raabe, D. S. Akad, et al. “Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission.” Journal of Neuroscience 33, no. 39 (September 25, 2013): 15504–15517. https://orcid.org/0000-0001-7060-0288 https://orcid.org/0000-0003-0096-2288 en_US http://dx.doi.org/10.1523/jneurosci.0019-12.2013 Journal of Neuroscience Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Society for Neuroscience Society for Neuroscience |
| spellingShingle | Kruger, Juliane M. Favaro, Plinio D. Liu, Mingna Kitlinska, Agata Huang, Xiaojie Raabe, Monika Akad, Derya S. Liu, Yanling Urlaub, Henning Dong, Yan Xu, Weifeng Schluter, Oliver M. Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission |
| title | Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission |
| title_full | Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission |
| title_fullStr | Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission |
| title_full_unstemmed | Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission |
| title_short | Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission |
| title_sort | differential roles of postsynaptic density 93 isoforms in regulating synaptic transmission |
| url | http://hdl.handle.net/1721.1/89137 https://orcid.org/0000-0001-7060-0288 https://orcid.org/0000-0003-0096-2288 |
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