PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density
PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. Here we show that PSD-95 is in an extended configuration and positioned into regular arrays of vertical filaments that contact bo...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Society for Neuroscience
2011
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| Online Access: | http://hdl.handle.net/1721.1/66976 |
| _version_ | 1826216493942046720 |
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| author | Chen, Xiaobing Nelson, Christopher D. Li, Xiang Winters, Christine A. Azzam, Rita Sousa, Alioscka A. Leapman, Richard D. Gainer, Harold Sheng, Morgan Hwa-Tze Reese, Thomas S. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Chen, Xiaobing Nelson, Christopher D. Li, Xiang Winters, Christine A. Azzam, Rita Sousa, Alioscka A. Leapman, Richard D. Gainer, Harold Sheng, Morgan Hwa-Tze Reese, Thomas S. |
| author_sort | Chen, Xiaobing |
| collection | MIT |
| description | PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. Here we show that PSD-95 is in an extended configuration and positioned into regular arrays of vertical filaments that contact both glutamate receptors and orthogonal horizontal elements layered deep inside the PSD in rat hippocampal spine synapses. RNA interference knockdown of PSD-95 leads to loss of entire patches of PSD material, and electron microscopy tomography shows that the patchy loss correlates with loss of PSD-95-containing vertical filaments, horizontal elements associated with the vertical filaments, and putative AMPA receptor-type, but not NMDA receptor-type, structures. These observations show that the orthogonal molecular scaffold constructed from PSD-95-containing vertical filaments and their associated horizontal elements is essential for sustaining the three-dimensional molecular organization of the PSD. Our findings provide a structural basis for understanding the functional role of PSD-95 at the PSD. |
| first_indexed | 2024-09-23T16:48:36Z |
| format | Article |
| id | mit-1721.1/66976 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:48:36Z |
| publishDate | 2011 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/669762022-10-03T08:26:58Z PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density Chen, Xiaobing Nelson, Christopher D. Li, Xiang Winters, Christine A. Azzam, Rita Sousa, Alioscka A. Leapman, Richard D. Gainer, Harold Sheng, Morgan Hwa-Tze Reese, Thomas S. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Sheng, Morgan Hwa-Tze Nelson, Christopher D. Sheng, Morgan Hwa-Tze PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. Here we show that PSD-95 is in an extended configuration and positioned into regular arrays of vertical filaments that contact both glutamate receptors and orthogonal horizontal elements layered deep inside the PSD in rat hippocampal spine synapses. RNA interference knockdown of PSD-95 leads to loss of entire patches of PSD material, and electron microscopy tomography shows that the patchy loss correlates with loss of PSD-95-containing vertical filaments, horizontal elements associated with the vertical filaments, and putative AMPA receptor-type, but not NMDA receptor-type, structures. These observations show that the orthogonal molecular scaffold constructed from PSD-95-containing vertical filaments and their associated horizontal elements is essential for sustaining the three-dimensional molecular organization of the PSD. Our findings provide a structural basis for understanding the functional role of PSD-95 at the PSD. National Institute of Neurological Disorders and Stroke (U.S.) National Institute of Biomedical Imaging and Bioengineering (U.S.) Howard Hughes Medical Institute 2011-11-09T16:01:08Z 2011-11-09T16:01:08Z 2011-03 2011-03 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/66976 Chen, X. et al. “PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density.” Journal of Neuroscience 31 (2011): 6329-6338. en_US http://dx.doi.org/10.1523/jneurosci.5968-10.2011 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 SFN |
| spellingShingle | Chen, Xiaobing Nelson, Christopher D. Li, Xiang Winters, Christine A. Azzam, Rita Sousa, Alioscka A. Leapman, Richard D. Gainer, Harold Sheng, Morgan Hwa-Tze Reese, Thomas S. PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density |
| title | PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density |
| title_full | PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density |
| title_fullStr | PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density |
| title_full_unstemmed | PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density |
| title_short | PSD-95 Is Required to Sustain the Molecular Organization of the Postsynaptic Density |
| title_sort | psd 95 is required to sustain the molecular organization of the postsynaptic density |
| url | http://hdl.handle.net/1721.1/66976 |
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