Journal article
SAP102 Mediates Synaptic Clearance of NMDA Receptors
Cell reports (Cambridge), v 2(5), pp 1120-1128
01 Nov 2012
PMID: 23103165
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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Details
- Title
- SAP102 Mediates Synaptic Clearance of NMDA Receptors
- Creators
- Bo-Shiun Chen - National Institute of Neurological Disorders and StrokeJohn A. Gray - Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USAAntonio Sanz-Clemente - National Institutes of HealthZhe Wei - College Station Medical CenterEleanor V. Thomas - National Institutes of HealthRoger A. Nicoll - University of California, San FranciscoKatherine W. Roche - National Institutes of Health
- Publication Details
- Cell reports (Cambridge), v 2(5), pp 1120-1128
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- NINDS Intramural Research Program; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) K08MH100562 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R00NS057266 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) NIMH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) NINDS Career Transition Award; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) NARSAD Young Investigator Award; NARSAD
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000314457700008
- Scopus ID
- 2-s2.0-84870411807
- Other Identifier
- 991020100202204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology