Divalent Cations Modulate the Activity of Metabotropic Glutamate Receptors

Anna Francesconi, Robert M. Duvoisin

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Metabotropic glutamate receptors (mGluRs) and calcium receptors (CaR) are closely related G protein-coupled receptors (GPCRs). The similar structural and functional properties of mGluRs and CaRs include conserved amino acid residues involved in glutamate binding in mGluRs and Ca2+ binding in the CaR. Furthermore, recent findings have demonstrated that mGluRs can respond to high extracellular Ca2+ (Ca2+o) whereas CaR activity is potentiated by L-amino acids. We show that both mGluR1 and mGluR2 are activated by Ca2+o in the absence of glutamate in the extracellular media. This activation by Ca2+o is antagonized by Mg2+o. Unlike the CaR, in which the intracellular carboxyl tail has been reported to be involved in Ca 2+o-dependent activity, the carboxyl tail of mGluRs does not seem to play a role in mediating Ca2+o actions. On the other hand, we find that preservation of disulfide bonds in the N-terminal extracellular domain of mGluRs is essential for stimulation by Ca 2+o as well as glutamate. Because the mGluR1 EC 50 for Ca2+o is within the physiologic range of Ca2+ in the synaptic cleft, mGluR function is likely regulated by changes in divalent cations caused by synaptic activity under normal or pathologic conditions.

Original languageEnglish (US)
Pages (from-to)472-479
Number of pages8
JournalJournal of Neuroscience Research
Volume75
Issue number4
DOIs
StatePublished - Feb 15 2004

Fingerprint

Metabotropic Glutamate Receptors
Divalent Cations
Calcium-Sensing Receptors
Glutamic Acid
Amino Acids
G-Protein-Coupled Receptors
Disulfides

Keywords

  • Calcium
  • Magnesium
  • MGluR
  • Zinc

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Divalent Cations Modulate the Activity of Metabotropic Glutamate Receptors. / Francesconi, Anna; Duvoisin, Robert M.

In: Journal of Neuroscience Research, Vol. 75, No. 4, 15.02.2004, p. 472-479.

Research output: Contribution to journalArticle

@article{65ea4e4f62954285a69b48c9f06b61ab,
title = "Divalent Cations Modulate the Activity of Metabotropic Glutamate Receptors",
abstract = "Metabotropic glutamate receptors (mGluRs) and calcium receptors (CaR) are closely related G protein-coupled receptors (GPCRs). The similar structural and functional properties of mGluRs and CaRs include conserved amino acid residues involved in glutamate binding in mGluRs and Ca2+ binding in the CaR. Furthermore, recent findings have demonstrated that mGluRs can respond to high extracellular Ca2+ (Ca2+o) whereas CaR activity is potentiated by L-amino acids. We show that both mGluR1 and mGluR2 are activated by Ca2+o in the absence of glutamate in the extracellular media. This activation by Ca2+o is antagonized by Mg2+o. Unlike the CaR, in which the intracellular carboxyl tail has been reported to be involved in Ca 2+o-dependent activity, the carboxyl tail of mGluRs does not seem to play a role in mediating Ca2+o actions. On the other hand, we find that preservation of disulfide bonds in the N-terminal extracellular domain of mGluRs is essential for stimulation by Ca 2+o as well as glutamate. Because the mGluR1 EC 50 for Ca2+o is within the physiologic range of Ca2+ in the synaptic cleft, mGluR function is likely regulated by changes in divalent cations caused by synaptic activity under normal or pathologic conditions.",
keywords = "Calcium, Magnesium, MGluR, Zinc",
author = "Anna Francesconi and Duvoisin, {Robert M.}",
year = "2004",
month = "2",
day = "15",
doi = "10.1002/jnr.10853",
language = "English (US)",
volume = "75",
pages = "472--479",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Divalent Cations Modulate the Activity of Metabotropic Glutamate Receptors

AU - Francesconi, Anna

AU - Duvoisin, Robert M.

PY - 2004/2/15

Y1 - 2004/2/15

N2 - Metabotropic glutamate receptors (mGluRs) and calcium receptors (CaR) are closely related G protein-coupled receptors (GPCRs). The similar structural and functional properties of mGluRs and CaRs include conserved amino acid residues involved in glutamate binding in mGluRs and Ca2+ binding in the CaR. Furthermore, recent findings have demonstrated that mGluRs can respond to high extracellular Ca2+ (Ca2+o) whereas CaR activity is potentiated by L-amino acids. We show that both mGluR1 and mGluR2 are activated by Ca2+o in the absence of glutamate in the extracellular media. This activation by Ca2+o is antagonized by Mg2+o. Unlike the CaR, in which the intracellular carboxyl tail has been reported to be involved in Ca 2+o-dependent activity, the carboxyl tail of mGluRs does not seem to play a role in mediating Ca2+o actions. On the other hand, we find that preservation of disulfide bonds in the N-terminal extracellular domain of mGluRs is essential for stimulation by Ca 2+o as well as glutamate. Because the mGluR1 EC 50 for Ca2+o is within the physiologic range of Ca2+ in the synaptic cleft, mGluR function is likely regulated by changes in divalent cations caused by synaptic activity under normal or pathologic conditions.

AB - Metabotropic glutamate receptors (mGluRs) and calcium receptors (CaR) are closely related G protein-coupled receptors (GPCRs). The similar structural and functional properties of mGluRs and CaRs include conserved amino acid residues involved in glutamate binding in mGluRs and Ca2+ binding in the CaR. Furthermore, recent findings have demonstrated that mGluRs can respond to high extracellular Ca2+ (Ca2+o) whereas CaR activity is potentiated by L-amino acids. We show that both mGluR1 and mGluR2 are activated by Ca2+o in the absence of glutamate in the extracellular media. This activation by Ca2+o is antagonized by Mg2+o. Unlike the CaR, in which the intracellular carboxyl tail has been reported to be involved in Ca 2+o-dependent activity, the carboxyl tail of mGluRs does not seem to play a role in mediating Ca2+o actions. On the other hand, we find that preservation of disulfide bonds in the N-terminal extracellular domain of mGluRs is essential for stimulation by Ca 2+o as well as glutamate. Because the mGluR1 EC 50 for Ca2+o is within the physiologic range of Ca2+ in the synaptic cleft, mGluR function is likely regulated by changes in divalent cations caused by synaptic activity under normal or pathologic conditions.

KW - Calcium

KW - Magnesium

KW - MGluR

KW - Zinc

UR - http://www.scopus.com/inward/record.url?scp=0742305129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0742305129&partnerID=8YFLogxK

U2 - 10.1002/jnr.10853

DO - 10.1002/jnr.10853

M3 - Article

C2 - 14743430

AN - SCOPUS:0742305129

VL - 75

SP - 472

EP - 479

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 4

ER -