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SAP102 mediates synaptic clearance of NMDA receptors.

Authors
  • Chen, Bo-Shiun1
  • Gray, John A
  • Sanz-Clemente, Antonio
  • Wei, Zhe
  • Thomas, Eleanor V
  • Nicoll, Roger A
  • Roche, Katherine W
  • 1 National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. [email protected] , (Georgia)
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Nov 29, 2012
Volume
2
Issue
5
Pages
1120–1128
Identifiers
DOI: 10.1016/j.celrep.2012.09.024
PMID: 23103165
Source
Medline
License
Unknown

Abstract

Membrane-associated guanylate kinases (MAGUKs) are the major family of scaffolding proteins at the postsynaptic density. The PSD-MAGUK subfamily, which includes PSD-95, PSD-93, SAP97, and SAP102, is well accepted to be primarily involved in the synaptic anchoring of numerous proteins, including N-methyl-D-aspartate receptors (NMDARs). Notably, the synaptic targeting of NMDARs depends on the binding of the PDZ ligand on the GluN2B subunit to MAGUK PDZ domains, as disruption of this interaction dramatically decreases NMDAR surface and synaptic expression. We recently reported a secondary interaction between SAP102 and GluN2B, in addition to the PDZ interaction. Here, we identify two critical residues on GluN2B responsible for the non-PDZ binding to SAP102. Strikingly, either mutation of these critical residues or knockdown of endogenous SAP102 can rescue the defective surface expression and synaptic localization of PDZ binding-deficient GluN2B. These data reveal an unexpected, nonscaffolding role for SAP102 in the synaptic clearance of GluN2B-containing NMDARs.

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