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NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex

Nature Cell Biology volume 5, pages 520–530 (2003)Cite this article

Abstract

NMDA (N-methyl-D-aspartate) receptors (NMDARs) are targeted to dendrites and anchored at the post-synaptic density (PSD) through interactions with PDZ proteins. However, little is known about how these receptors are sorted from the endoplasmic reticulum and Golgi apparatus to the synapse. Here, we find that synapse-associated protein 102 (SAP102) interacts with the PDZ-binding domain of Sec8, a member of the exocyst complex. Our results show that interactions between SAP102 and Sec8 are involved in the delivery of NMDARs to the cell surface in heterologous cells and neurons. Furthermore, they suggest that an exocyst–SAP102–NMDAR complex is an important component of NMDAR trafficking.

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Figure 1: Direct interaction between SAP102 PDZ domains and Sec8.
Figure 2: Exocyst, SAP102 and NMDAR form a complex in brain.
Figure 3: Ultrastructure of the Sec6–Sec8 association in neurons.
Figure 4: Effect of transfected Sec8WT or Sec8Δ4 on NMDAR distribution in COS cells.
Figure 6: Association of NR2B and Sec8WT in the endoplasmic reticulum of transfected cells.
Figure 5: Effect of transfected Sec8WT/Sec8Δ4 on NMDAR distribution in heterologous cells.
Figure 7: Effect of Sec8Δ4 on NMDAR distribution in neurons.
Figure 8: The exocyst complex and the delivery of NMDARs to the cell surface.

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Acknowledgements

We thank C.C. Garner for providing the SAP102 cDNA, S.C. Hsu for providing the Sec6 and Sec8 cDNAs and the GST–Exo70 and Sec10 constructs, J.H. Luo for the YFP–NR1-1 construct, A. de Blas for the GABAAR anti-α1 antibody and β3 cDNA, F.A. Stephenson for the Myc- and Flag-tagged NR2B constructs and R.L. Huganir for the GRIP antibody. We would also like to thank C.Y. Wang, L. Hawkins, S. Standley and M. Montcouquiol for helpful comments and discussion, P. Wang for excellent technical assistance, and Z. Fu and G. Losi for cerebellar granule cell cultures. Animals were handled in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH publication 85–23; NIDCD protocol #1022-01). This work was supported by the National institute of deafness and other communication disorders (NIDCD), Pharmacology research associate (PRAT) Fellowship Program (National institute of general medical sciences (NIGMS), K.P.), and National institute of mental health (NIMH, S.V.).

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Authors and Affiliations

  1. Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Building 50, Room 4146, 50 South Drive, Bethesda, 20892-8027, MD, USA

    Nathalie Sans, Kate Prybylowski, Ronald S. Petralia, Kai Chang, Ya-Xian Wang, Claudia Racca & Robert J. Wenthold

  2. Department of Physiology and Biophysics, Georgetown University Medical Center, Room BSB225, 3900 Reservoir Road NW, Washington, 20057-1421, DC, USA

    Stefano Vicini

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Sans, N., Prybylowski, K., Petralia, R. et al. NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex. Nat Cell Biol 5, 520–530 (2003). https://doi.org/10.1038/ncb990

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