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PSD-95 is required to sustain the molecular organization of the postsynaptic density.

Authors: Chen, X  Nelson, CD  Li, X  Winters, CA  Azzam, R  Sousa, AA  Leapman, RD  Gainer, H  Sheng, M  Reese, TS 
Citation: Chen X, etal., J Neurosci. 2011 Apr 27;31(17):6329-38. doi: 10.1523/JNEUROSCI.5968-10.2011.
Pubmed: (View Article at PubMed) PMID:21525273
DOI: Full-text: DOI:10.1523/JNEUROSCI.5968-10.2011

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.

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CRRD Object Information
CRRD ID: 8554095
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.