Editors' ChoiceNeuroscience

Exocyst Escort for NMDA Receptor

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Science's STKE  10 Jun 2003:
Vol. 2003, Issue 186, pp. tw218-TW218
DOI: 10.1126/stke.2003.186.tw218

NMDA (N-methyl-D-aspartate) receptors for the excitatory neurotransmitter glutamate are anchored at synapses through interactions with cytoplasmic scaffold proteins. A two-hybrid screen for proteins that interacts with one such scaffold, SAP102 (synapse-associated protein), yielded an interaction partner that may help explain how trafficking of NMDA receptors to the cell surface is controlled. Sans et al. detected interaction of SAP102 with Sec8, a protein most studied in yeast where it is a component of the exocyst complex, which functions to promote fusion of membrane vesicles to the plasma membrane and thus confirmed the existence of the complex in rat brain. In Cos cells or cultured hippocampal neurons, overexpression of a dominant-negative Sec8 protein inhibited delivery of NMDA receptors to the cell surface. When overexpressed with the NR2B NMDA receptor subunit in Cos cells, Sec8 localized with the receptor not only at the plasma membrane, but also in the endoplasmic reticulum. If the dominant-negative Sec8 was used in similar experiments, delivery of newly synthesized NRB2 to the plasma membrane was inhibited. The results emphasize that scaffold proteins serve not only to anchor and regulate receptors at the cell surface, but also to control delivery of the receptor to the cell surface. Such regulation of receptor abundance is thought to underlie long-term changes in synaptic function that serve as the basis for learning and memory. Hoogenraad and Sheng provide commentary on the paper.

N. Sans, K. Prybylowski, R. S. Petralia, K. Chang, Y.-X. Wang, C. Racca, S. Vicini, R. J. Wenthold, NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex. Nat. Cell Biol. 5, 520-530 (2003). [Online Journal]

C. C. Hoogenraad, M. Sheng, The return of the exocyst. Nat. Cell Biol. 5, 493-495 (2003). [Online Journal]

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