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

318 Citations (Scopus)

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 - 2001

Fingerprint

N-Methyl-D-Aspartate Receptors
Protein Kinase C
Exocytosis
N-Methylaspartate
Fluorescent Antibody Technique
Synaptosomal-Associated Protein 25
Neurons
SNARE Proteins
Dendritic Spines
Type A Botulinum Toxins
Neuronal Plasticity
Electrophysiology
Dendrites
Xenopus
Synaptic Transmission
Protein Kinases
Oocytes
Cell Membrane

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lan, J. Y., Skeberdis, V. A., Jover, T., Grooms, S. Y., Lin, Y., Araneda, R. C., ... 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

Protein kinase C modulates NMDA receptor trafficking and gating. / Lan, Jian Yu; Skeberdis, Vytenis A.; Jover, Teresa; Grooms, Sonja Y.; Lin, Ying; Araneda, Ricardo C.; Zheng, Xin; Bennett, Michael V. L.; Zukin, R. Suzanne.

In: Nature Neuroscience, Vol. 4, No. 4, 2001, p. 382-390.

Research output: Contribution to journalArticle

Lan, JY, Skeberdis, VA, Jover, T, Grooms, SY, Lin, Y, Araneda, RC, Zheng, X, Bennett, MVL & Zukin, RS 2001, 'Protein kinase C modulates NMDA receptor trafficking and gating', Nature Neuroscience, vol. 4, no. 4, pp. 382-390. https://doi.org/10.1038/86028
Lan JY, Skeberdis VA, Jover T, Grooms SY, Lin Y, Araneda RC et al. Protein kinase C modulates NMDA receptor trafficking and gating. Nature Neuroscience. 2001;4(4):382-390. https://doi.org/10.1038/86028
Lan, Jian Yu ; Skeberdis, Vytenis A. ; Jover, Teresa ; Grooms, Sonja Y. ; Lin, Ying ; Araneda, Ricardo C. ; Zheng, Xin ; Bennett, Michael V. L. ; Zukin, R. Suzanne. / Protein kinase C modulates NMDA receptor trafficking and gating. In: Nature Neuroscience. 2001 ; Vol. 4, No. 4. pp. 382-390.
@article{3fa3323e93244d09a73ef51e016cabb5,
title = "Protein kinase C modulates NMDA receptor trafficking and gating",
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.",
author = "Lan, {Jian Yu} and Skeberdis, {Vytenis A.} and Teresa Jover and Grooms, {Sonja Y.} and Ying Lin and Araneda, {Ricardo C.} and Xin Zheng and Bennett, {Michael V. L.} and Zukin, {R. Suzanne}",
year = "2001",
doi = "10.1038/86028",
language = "English (US)",
volume = "4",
pages = "382--390",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Protein kinase C modulates NMDA receptor trafficking and gating

AU - Lan, Jian Yu

AU - Skeberdis, Vytenis A.

AU - Jover, Teresa

AU - Grooms, Sonja Y.

AU - Lin, Ying

AU - Araneda, Ricardo C.

AU - Zheng, Xin

AU - Bennett, Michael V. L.

AU - Zukin, R. Suzanne

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035094057&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035094057&partnerID=8YFLogxK

U2 - 10.1038/86028

DO - 10.1038/86028

M3 - Article

VL - 4

SP - 382

EP - 390

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 4

ER -