Protein kinase C modulates NMDA receptor trafficking and gating

Jian Yu Lan, Vytenis A. Skeberdis, Teresa Jover, Sonja Y. Grooms, Ying Lin, Ricardo C. Araneda, Xin Zheng, Michael V.L. Bennett, R. Suzanne Zukin

Research output: Contribution to journalArticle

329 Scopus citations

Abstract

Regulation of neuronal N-methyl-D-aspartate receptors (NMDARs) by protein kinases is critical in synaptic transmission. However, the molecular mechanisms underlying protein kinase C (PKC) potentiation of NMDARs are uncertain. Here we demonstrate that PKC increases NMDA channel opening rate and delivers new NMDA channels to the plasma membrane through regulated exocytosis. PKC induced a rapid delivery of functional NMDARs to the cell surface and increased surface NR1 immunofluorescence in Xenopus oocytes expressing NMDARs. PKC potentiation was inhibited by botulinum neurotoxin A and a dominant negative mutant of soluble NSF-associated protein (SNAP-25), suggesting that receptor trafficking occurs via SNARE-dependent exocytosis. In neurons, PKC induced a rapid delivery of functional NMDARs, assessed by electrophysiology, and an increase in NMDAR clusters on the surface of dendrites and dendritic spines, as indicated by immunofluorescence. Thus, PKC regulates NMDAR channel gating and trafficking in recombinant systems and in neurons, mechanisms that may be relevant to synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)382-390
Number of pages9
JournalNature Neuroscience
Volume4
Issue number4
DOIs
StatePublished - Apr 12 2001

ASJC Scopus subject areas

  • Neuroscience(all)

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    Lan, J. Y., Skeberdis, V. A., Jover, T., Grooms, S. Y., Lin, Y., Araneda, R. C., Zheng, X., Bennett, M. V. L., & Zukin, R. S. (2001). Protein kinase C modulates NMDA receptor trafficking and gating. Nature Neuroscience, 4(4), 382-390. https://doi.org/10.1038/86028