Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses
PSD-95-like, disc-large (DLG) family membrane-associated guanylate kinase proteins (PSD/DLG-MAGUKs) are essential for regulating synaptic AMPA receptor (AMPAR) function and activity-dependent trafficking of AMPARs. Using a molecular replacement strategy to replace endogenous PSD-95 with SAP97β, we s...
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| Language: | en_US |
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American Physiological Society
2015
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| Online Access: | http://hdl.handle.net/1721.1/93904 https://orcid.org/0000-0001-6888-5448 https://orcid.org/0000-0003-2668-7819 https://orcid.org/0000-0001-7060-0288 https://orcid.org/0000-0003-0096-2288 |
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| author | Liu, Mingna Lewis, Laura D. Shi, Rebecca D. Xu, Weifeng Brown, Emery Neal |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Liu, Mingna Lewis, Laura D. Shi, Rebecca D. Xu, Weifeng Brown, Emery Neal |
| author_sort | Liu, Mingna |
| collection | MIT |
| description | PSD-95-like, disc-large (DLG) family membrane-associated guanylate kinase proteins (PSD/DLG-MAGUKs) are essential for regulating synaptic AMPA receptor (AMPAR) function and activity-dependent trafficking of AMPARs. Using a molecular replacement strategy to replace endogenous PSD-95 with SAP97β, we show that the prototypic β-isoform of the PSD-MAGUKs, SAP97β, has distinct NMDA receptor (NMDAR)-dependent roles in regulating basic properties of AMPAR-containing synapses. SAP97β enhances the number of AMPAR-containing synapses in an NMDAR-dependent manner, whereas its effect on the size of unitary synaptic response is not fully dependent on NMDAR activity. These effects contrast with those of PSD-95α, which increases both the number of AMPAR-containing synapses and the size of unitary synaptic responses, with or without NMDAR activity. Our results suggest that SAP97β regulates synaptic AMPAR content by increasing surface expression of GluA1-containing AMPARs, whereas PSD-95α enhances synaptic AMPAR content presumably by increasing the synaptic scaffold capacity for synaptic AMPARs. Our approach delineates discrete effects of different PSD-MAGUKs on principal properties of glutamatergic synaptic transmission. Our results suggest that the molecular diversity of PSD-MAGUKs can provide rich molecular substrates for differential regulation of glutamatergic synapses in the brain. |
| first_indexed | 2024-09-23T14:03:03Z |
| format | Article |
| id | mit-1721.1/93904 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:03:03Z |
| publishDate | 2015 |
| publisher | American Physiological Society |
| record_format | dspace |
| spelling | mit-1721.1/939042022-09-28T17:57:51Z Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses Liu, Mingna Lewis, Laura D. Shi, Rebecca D. Xu, Weifeng Brown, Emery Neal Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Brown, Emery N. Liu, Mingna Lewis, Laura D. Shi, Rebecca D. Brown, Emery N. Xu, Weifeng PSD-95-like, disc-large (DLG) family membrane-associated guanylate kinase proteins (PSD/DLG-MAGUKs) are essential for regulating synaptic AMPA receptor (AMPAR) function and activity-dependent trafficking of AMPARs. Using a molecular replacement strategy to replace endogenous PSD-95 with SAP97β, we show that the prototypic β-isoform of the PSD-MAGUKs, SAP97β, has distinct NMDA receptor (NMDAR)-dependent roles in regulating basic properties of AMPAR-containing synapses. SAP97β enhances the number of AMPAR-containing synapses in an NMDAR-dependent manner, whereas its effect on the size of unitary synaptic response is not fully dependent on NMDAR activity. These effects contrast with those of PSD-95α, which increases both the number of AMPAR-containing synapses and the size of unitary synaptic responses, with or without NMDAR activity. Our results suggest that SAP97β regulates synaptic AMPAR content by increasing surface expression of GluA1-containing AMPARs, whereas PSD-95α enhances synaptic AMPAR content presumably by increasing the synaptic scaffold capacity for synaptic AMPARs. Our approach delineates discrete effects of different PSD-MAGUKs on principal properties of glutamatergic synaptic transmission. Our results suggest that the molecular diversity of PSD-MAGUKs can provide rich molecular substrates for differential regulation of glutamatergic synapses in the brain. National Institutes of Health (U.S.) (Grant MH080310) National Institutes of Health (U.S.) (Transformative Research Award R01 GM104948-02) 2015-02-06T17:05:04Z 2015-02-06T17:05:04Z 2013-11 2013-11 Article http://purl.org/eprint/type/JournalArticle 0022-3077 1522-1598 http://hdl.handle.net/1721.1/93904 Liu, M., L. D. Lewis, R. Shi, E. N. Brown, and W. Xu. “Differential Requirement for NMDAR Activity in SAP97 -Mediated Regulation of the Number and Strength of Glutamatergic AMPAR-Containing Synapses.” Journal of Neurophysiology 111, no. 3 (November 13, 2013): 648–658. https://orcid.org/0000-0001-6888-5448 https://orcid.org/0000-0003-2668-7819 https://orcid.org/0000-0001-7060-0288 https://orcid.org/0000-0003-0096-2288 en_US http://dx.doi.org/10.1152/jn.00262.2013 Journal of Neurophysiology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Physiological Society Brown via Courtney Crummett |
| spellingShingle | Liu, Mingna Lewis, Laura D. Shi, Rebecca D. Xu, Weifeng Brown, Emery Neal Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses |
| title | Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses |
| title_full | Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses |
| title_fullStr | Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses |
| title_full_unstemmed | Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses |
| title_short | Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses |
| title_sort | differential requirement for nmdar activity in sap97 mediated regulation of the number and strength of glutamatergic ampar containing synapses |
| url | http://hdl.handle.net/1721.1/93904 https://orcid.org/0000-0001-6888-5448 https://orcid.org/0000-0003-2668-7819 https://orcid.org/0000-0001-7060-0288 https://orcid.org/0000-0003-0096-2288 |
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