SAP102 Mediates Synaptic Clearance of NMDA Receptors

Bo-Shiun Chen, John A. Gray, Antonio Sanz-Clemente, Zhe Wei, Eleanor V. Thomas, Roger A. Nicoll, Katherine W. Roche

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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.

Original languageEnglish (US)
Pages (from-to)1120-1128
Number of pages9
JournalCell Reports
Volume2
Issue number5
DOIs
StatePublished - Nov 29 2012

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Guanylate Kinases
N-Methyl-D-Aspartate Receptors
PDZ Domains
Proteins
Ligands
Mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chen, B-S., Gray, J. A., Sanz-Clemente, A., Wei, Z., Thomas, E. V., Nicoll, R. A., & Roche, K. W. (2012). SAP102 Mediates Synaptic Clearance of NMDA Receptors. Cell Reports, 2(5), 1120-1128. https://doi.org/10.1016/j.celrep.2012.09.024

SAP102 Mediates Synaptic Clearance of NMDA Receptors. / Chen, Bo-Shiun; Gray, John A.; Sanz-Clemente, Antonio; Wei, Zhe; Thomas, Eleanor V.; Nicoll, Roger A.; Roche, Katherine W.

In: Cell Reports, Vol. 2, No. 5, 29.11.2012, p. 1120-1128.

Research output: Contribution to journalArticle

Chen, B-S, Gray, JA, Sanz-Clemente, A, Wei, Z, Thomas, EV, Nicoll, RA & Roche, KW 2012, 'SAP102 Mediates Synaptic Clearance of NMDA Receptors', Cell Reports, vol. 2, no. 5, pp. 1120-1128. https://doi.org/10.1016/j.celrep.2012.09.024
Chen B-S, Gray JA, Sanz-Clemente A, Wei Z, Thomas EV, Nicoll RA et al. SAP102 Mediates Synaptic Clearance of NMDA Receptors. Cell Reports. 2012 Nov 29;2(5):1120-1128. https://doi.org/10.1016/j.celrep.2012.09.024
Chen, Bo-Shiun ; Gray, John A. ; Sanz-Clemente, Antonio ; Wei, Zhe ; Thomas, Eleanor V. ; Nicoll, Roger A. ; Roche, Katherine W. / SAP102 Mediates Synaptic Clearance of NMDA Receptors. In: Cell Reports. 2012 ; Vol. 2, No. 5. pp. 1120-1128.
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