Activity-dependent regulation of surface glucose transporter-3

Jainne M. Ferreira, Arthur Burnett, Gerald A. Rameau

Research output: Contribution to journalArticle

Abstract

Glucose transporter 3 (GLUT3) is the main facilitative glucose transporter in neurons. Glucose provides neurons with a critical energy source for neuronal activity. However, the mechanism by which neuronal activity controls glucose influx via GLUT3 is unknown. We investigated the influence of synaptic stimulation on GLUT3 surface expression and glucose import in primary cultured cortical and hippocampal neurons. Synaptic activity increased surface expression of GLUT3 leading to an elevation of intracellular glucose. The effect was blocked by NMDA receptor (NMDAR) and neuronal nitric oxide synthase (nNOS) inhibition. The Akt inhibitor I (Akt-I) blocked NMDAR-induced GLUT3 surface expression while a nNOS-phosphomimetic mutant (S1412D) enhanced GLUT3 expression at cell surface. These results suggest that NMDAR/Akt-dependent nNOS phosphorylation is coupled to GLUT3 trafficking. We demonstrated that activation of cGMP-dependent protein kinase (cGK) increased the surface expression of GLUT3, which was repressed by Rp-8-pCPT-cGMPS, a potent cell-permeable inhibitor of cGKs. These studies characterize the molecular basis for activity-dependent increases in surface GLUT3 after stimulation of the NMDARs. NMDAR-induced increase in surface GLUT3 represents a novel pathway for control of energy supply during neuronal activity that is critical for maintaining glucose homeostasis during neuronal transmission.

Original languageEnglish (US)
Pages (from-to)1991-1999
Number of pages9
JournalJournal of Neuroscience
Volume31
Issue number6
DOIs
StatePublished - Feb 9 2011

Fingerprint

Facilitative Glucose Transport Proteins
N-Methyl-D-Aspartate Receptors
Nitric Oxide Synthase Type I
Glucose
Neurons
Cyclic GMP-Dependent Protein Kinases
Homeostasis
Phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activity-dependent regulation of surface glucose transporter-3. / Ferreira, Jainne M.; Burnett, Arthur; Rameau, Gerald A.

In: Journal of Neuroscience, Vol. 31, No. 6, 09.02.2011, p. 1991-1999.

Research output: Contribution to journalArticle

Ferreira, Jainne M. ; Burnett, Arthur ; Rameau, Gerald A. / Activity-dependent regulation of surface glucose transporter-3. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 6. pp. 1991-1999.
@article{243df4dd613549e98ef629fbaa46fe41,
title = "Activity-dependent regulation of surface glucose transporter-3",
abstract = "Glucose transporter 3 (GLUT3) is the main facilitative glucose transporter in neurons. Glucose provides neurons with a critical energy source for neuronal activity. However, the mechanism by which neuronal activity controls glucose influx via GLUT3 is unknown. We investigated the influence of synaptic stimulation on GLUT3 surface expression and glucose import in primary cultured cortical and hippocampal neurons. Synaptic activity increased surface expression of GLUT3 leading to an elevation of intracellular glucose. The effect was blocked by NMDA receptor (NMDAR) and neuronal nitric oxide synthase (nNOS) inhibition. The Akt inhibitor I (Akt-I) blocked NMDAR-induced GLUT3 surface expression while a nNOS-phosphomimetic mutant (S1412D) enhanced GLUT3 expression at cell surface. These results suggest that NMDAR/Akt-dependent nNOS phosphorylation is coupled to GLUT3 trafficking. We demonstrated that activation of cGMP-dependent protein kinase (cGK) increased the surface expression of GLUT3, which was repressed by Rp-8-pCPT-cGMPS, a potent cell-permeable inhibitor of cGKs. These studies characterize the molecular basis for activity-dependent increases in surface GLUT3 after stimulation of the NMDARs. NMDAR-induced increase in surface GLUT3 represents a novel pathway for control of energy supply during neuronal activity that is critical for maintaining glucose homeostasis during neuronal transmission.",
author = "Ferreira, {Jainne M.} and Arthur Burnett and Rameau, {Gerald A.}",
year = "2011",
month = "2",
day = "9",
doi = "10.1523/JNEUROSCI.1850-09.2011",
language = "English (US)",
volume = "31",
pages = "1991--1999",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "6",

}

TY - JOUR

T1 - Activity-dependent regulation of surface glucose transporter-3

AU - Ferreira, Jainne M.

AU - Burnett, Arthur

AU - Rameau, Gerald A.

PY - 2011/2/9

Y1 - 2011/2/9

N2 - Glucose transporter 3 (GLUT3) is the main facilitative glucose transporter in neurons. Glucose provides neurons with a critical energy source for neuronal activity. However, the mechanism by which neuronal activity controls glucose influx via GLUT3 is unknown. We investigated the influence of synaptic stimulation on GLUT3 surface expression and glucose import in primary cultured cortical and hippocampal neurons. Synaptic activity increased surface expression of GLUT3 leading to an elevation of intracellular glucose. The effect was blocked by NMDA receptor (NMDAR) and neuronal nitric oxide synthase (nNOS) inhibition. The Akt inhibitor I (Akt-I) blocked NMDAR-induced GLUT3 surface expression while a nNOS-phosphomimetic mutant (S1412D) enhanced GLUT3 expression at cell surface. These results suggest that NMDAR/Akt-dependent nNOS phosphorylation is coupled to GLUT3 trafficking. We demonstrated that activation of cGMP-dependent protein kinase (cGK) increased the surface expression of GLUT3, which was repressed by Rp-8-pCPT-cGMPS, a potent cell-permeable inhibitor of cGKs. These studies characterize the molecular basis for activity-dependent increases in surface GLUT3 after stimulation of the NMDARs. NMDAR-induced increase in surface GLUT3 represents a novel pathway for control of energy supply during neuronal activity that is critical for maintaining glucose homeostasis during neuronal transmission.

AB - Glucose transporter 3 (GLUT3) is the main facilitative glucose transporter in neurons. Glucose provides neurons with a critical energy source for neuronal activity. However, the mechanism by which neuronal activity controls glucose influx via GLUT3 is unknown. We investigated the influence of synaptic stimulation on GLUT3 surface expression and glucose import in primary cultured cortical and hippocampal neurons. Synaptic activity increased surface expression of GLUT3 leading to an elevation of intracellular glucose. The effect was blocked by NMDA receptor (NMDAR) and neuronal nitric oxide synthase (nNOS) inhibition. The Akt inhibitor I (Akt-I) blocked NMDAR-induced GLUT3 surface expression while a nNOS-phosphomimetic mutant (S1412D) enhanced GLUT3 expression at cell surface. These results suggest that NMDAR/Akt-dependent nNOS phosphorylation is coupled to GLUT3 trafficking. We demonstrated that activation of cGMP-dependent protein kinase (cGK) increased the surface expression of GLUT3, which was repressed by Rp-8-pCPT-cGMPS, a potent cell-permeable inhibitor of cGKs. These studies characterize the molecular basis for activity-dependent increases in surface GLUT3 after stimulation of the NMDARs. NMDAR-induced increase in surface GLUT3 represents a novel pathway for control of energy supply during neuronal activity that is critical for maintaining glucose homeostasis during neuronal transmission.

UR - http://www.scopus.com/inward/record.url?scp=79951540531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951540531&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1850-09.2011

DO - 10.1523/JNEUROSCI.1850-09.2011

M3 - Article

VL - 31

SP - 1991

EP - 1999

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 6

ER -