Abstract |
Activity-dependent regulation of AMPA receptor (AMPAR)-mediated synaptic transmission is the basis for establishing differences in synaptic weights among individual synapses during developmental and experience-dependent synaptic plasticity. Synaptic signaling scaffolds of the Discs large (DLG)- membrane-associated guanylate kinase (MAGUK) protein family regulate these processes by tethering signaling proteins to receptor complexes. Using a molecular replacement strategy with RNAi-mediated knockdown in rat and mouse hippocampal organotypic slice cultures, a postsynaptic density-95 (PSD-95) knock-out mouse line and electrophysiological analysis, our current study identified a functional interplay between two paralogs, PSD-95 and synapse-associated protein 102 (SAP102) to regulate synaptic AMPARs. During synaptic development, the SAP102 protein levels normally plateau but double if PSD-95 expression is prevented during synaptogenesis. For an autonomous function of PSD-95 in regulating synaptic AMPARs, in addition to the previously demonstrated N-terminal multimerization and the first two PDZ (PSD-95, Dlg1, zona occludens-1) domains, the PDZ3 and guanylate kinase domains were required. The Src homology 3 domain was dispensable for the PSD-95-autonomous regulation of basal synaptic transmission. However, it mediated the functional interaction with SAP102 of PSD-95 mutants to enhance AMPARs. These results depict a protein domain-based multifunctional aspect of PSD-95 in regulating excitatory synaptic transmission and unveil a novel form of domain-based interplay between signaling scaffolds of the DLG-MAGUK family.
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Authors | Stéphanie A D Bonnet, Derya S Akad, Tanmoy Samaddar, Yanling Liu, Xiaojie Huang, Yan Dong, Oliver M Schlüter |
Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience
(J Neurosci)
Vol. 33
Issue 33
Pg. 13398-409
(Aug 14 2013)
ISSN: 1529-2401 [Electronic] United States |
PMID | 23946397
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Disks Large Homolog 4 Protein
- Dlg3 protein, rat
- Dlg4 protein, mouse
- Dlg4 protein, rat
- Intracellular Signaling Peptides and Proteins
- Membrane Proteins
- Neuropeptides
- Dlgh3 protein, mouse
- Guanylate Kinases
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Topics |
- Animals
- Blotting, Western
- Disks Large Homolog 4 Protein
- Female
- Gene Knockout Techniques
- Guanylate Kinases
(metabolism)
- Intracellular Signaling Peptides and Proteins
(metabolism)
- Male
- Membrane Proteins
(metabolism)
- Mice
- Neuropeptides
(metabolism)
- Organ Culture Techniques
- Patch-Clamp Techniques
- Rats
- Rats, Wistar
- Synapses
(metabolism)
- Synaptic Transmission
(physiology)
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