Differential requirement for NMDAR activity in SAP97 -mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses
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Author(s)
Liu, Mingna
Lewis, Laura D.
Shi, Rebecca D.
Xu, Weifeng
Brown, Emery Neal
Date Issued
November 2013
Journal
Journal of Neurophysiology
Publisher
American Physiological Society
Citation
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.
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Abstract
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.
MIT Department
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
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DOI of Published Version
https://doi.org/10.1152/jn.00262.2013
