Insulin promotes rapid delivery of N-methyl-D-aspartate receptors to the cell surface by exocytosis

Vytenis A. Skeberdis, Jian Yu Lan, Xin Zheng, R. Suzanne Zukin, Michael V. L. Bennett

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

Insulin potentiates N-methyl-D-aspartate receptors (NMDARs) in neurons and Xenopus oocytes expressing recombinant NMDARs. The present study shows that insulin induced (i) an increase in channel number times open probability (nPo) in outside-out patches excised from Xenopus oocytes, with no change in mean open time, unitary conductance, or reversal potential, indicating an increase in n and/or Po;; (ii) an increase in charge transfer during block of NMDA-elicited currents by the open channel blocker MK-801, indicating increased number of functional NMDARs in the cell membrane with no change in Po;; and (iii) increased NR1 surface expression, as indicated by Western blot analysis of surface proteins. Botulinum neurotoxin A greatly reduced insulin potentiation, indicating that insertion of new receptors occurs via SNARE-dependent exocytosis. Thus, insulin potentiation occurs via delivery of new channels to the plasma membrane. NMDARs assembled from mutant subunits lacking all known sites of tyrosine and serine/threonine phosphorylation in their carboxyl-terminal tails exhibited robust insulin potentiation, suggesting that insulin potentiation does not require direct phosphorylation of NMDAR subunits. Because insulin and insulin receptors are localized to glutamatergic synapses in the hippocampus, insulin-regulated trafficking of NMDARs may play a role in synaptic transmission and plasticity, including long-term potentiation.

Original languageEnglish (US)
Pages (from-to)3561-3566
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number6
DOIs
StatePublished - Mar 13 2001

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Exocytosis
N-Methyl-D-Aspartate Receptors
Insulin
Xenopus
Oocytes
Phosphorylation
Cell Membrane
SNARE Proteins
Type A Botulinum Toxins
Neuronal Plasticity
Dizocilpine Maleate
Long-Term Potentiation
Insulin Receptor
N-Methylaspartate
Threonine
Synaptic Transmission
Synapses
Serine
Tyrosine
Tail

Keywords

  • Insulin receptor tyrosine kinase
  • Regulated exocytosis
  • Xenopus oocytes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Insulin promotes rapid delivery of N-methyl-D-aspartate receptors to the cell surface by exocytosis. / Skeberdis, Vytenis A.; Lan, Jian Yu; Zheng, Xin; Zukin, R. Suzanne; Bennett, Michael V. L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 6, 13.03.2001, p. 3561-3566.

Research output: Contribution to journalArticle

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