Genetic analysis of neuronal ionotropic glutamate receptor subunits

Adam J. Granger, John Gray, Wei Lu, Roger A. Nicoll

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

In the brain, fast, excitatory synaptic transmission occurs primarily through AMPA- and NMDA-type ionotropic glutamate receptors. These receptors are composed of subunit proteins that determine their biophysical properties and trafficking behaviour. Therefore, determining the function of these subunits and receptor subunit composition is essential for understanding the physiological properties of synaptic transmission. Here, we discuss and evaluate various genetic approaches that have been used to study AMPA and NMDA receptor subunits. These approaches have demonstrated that the GluA1 AMPA receptor subunit is required for activity-dependent trafficking and contributes to basal synaptic transmission, while the GluA2 subunit regulates Ca2+ permeability, homeostasis and trafficking to the synapse under basal conditions. In contrast, the GluN2A and GluN2B NMDA receptor subunits regulate synaptic AMPA receptor content, both during synaptic development and plasticity. Ongoing research in this field is focusing on the molecular interactions and mechanisms that control these functions. To accomplish this, molecular replacement techniques are being used, where native subunits are replaced with receptors containing targeted mutations. In this review, we discuss a single-cell molecular replacement approach which should arguably advance our physiological understanding of ionotropic glutamate receptor subunits, but is generally applicable to study of any neuronal protein.

Original languageEnglish (US)
Pages (from-to)4095-4101
Number of pages7
JournalJournal of Physiology
Volume589
Issue number17
DOIs
StatePublished - Sep 2011
Externally publishedYes

Fingerprint

Ionotropic Glutamate Receptors
AMPA Receptors
Synaptic Transmission
N-Methyl-D-Aspartate Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neurotransmitter Receptor
Neuronal Plasticity
Protein Subunits
N-Methylaspartate
Synapses
Permeability
Homeostasis
Mutation
Brain
Research
Proteins

ASJC Scopus subject areas

  • Physiology

Cite this

Genetic analysis of neuronal ionotropic glutamate receptor subunits. / Granger, Adam J.; Gray, John; Lu, Wei; Nicoll, Roger A.

In: Journal of Physiology, Vol. 589, No. 17, 09.2011, p. 4095-4101.

Research output: Contribution to journalArticle

Granger, Adam J. ; Gray, John ; Lu, Wei ; Nicoll, Roger A. / Genetic analysis of neuronal ionotropic glutamate receptor subunits. In: Journal of Physiology. 2011 ; Vol. 589, No. 17. pp. 4095-4101.
@article{6deacc9d14e0446faf5b5f02f9aad272,
title = "Genetic analysis of neuronal ionotropic glutamate receptor subunits",
abstract = "In the brain, fast, excitatory synaptic transmission occurs primarily through AMPA- and NMDA-type ionotropic glutamate receptors. These receptors are composed of subunit proteins that determine their biophysical properties and trafficking behaviour. Therefore, determining the function of these subunits and receptor subunit composition is essential for understanding the physiological properties of synaptic transmission. Here, we discuss and evaluate various genetic approaches that have been used to study AMPA and NMDA receptor subunits. These approaches have demonstrated that the GluA1 AMPA receptor subunit is required for activity-dependent trafficking and contributes to basal synaptic transmission, while the GluA2 subunit regulates Ca2+ permeability, homeostasis and trafficking to the synapse under basal conditions. In contrast, the GluN2A and GluN2B NMDA receptor subunits regulate synaptic AMPA receptor content, both during synaptic development and plasticity. Ongoing research in this field is focusing on the molecular interactions and mechanisms that control these functions. To accomplish this, molecular replacement techniques are being used, where native subunits are replaced with receptors containing targeted mutations. In this review, we discuss a single-cell molecular replacement approach which should arguably advance our physiological understanding of ionotropic glutamate receptor subunits, but is generally applicable to study of any neuronal protein.",
author = "Granger, {Adam J.} and John Gray and Wei Lu and Nicoll, {Roger A.}",
year = "2011",
month = "9",
doi = "10.1113/jphysiol.2011.213033",
language = "English (US)",
volume = "589",
pages = "4095--4101",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "17",

}

TY - JOUR

T1 - Genetic analysis of neuronal ionotropic glutamate receptor subunits

AU - Granger, Adam J.

AU - Gray, John

AU - Lu, Wei

AU - Nicoll, Roger A.

PY - 2011/9

Y1 - 2011/9

N2 - In the brain, fast, excitatory synaptic transmission occurs primarily through AMPA- and NMDA-type ionotropic glutamate receptors. These receptors are composed of subunit proteins that determine their biophysical properties and trafficking behaviour. Therefore, determining the function of these subunits and receptor subunit composition is essential for understanding the physiological properties of synaptic transmission. Here, we discuss and evaluate various genetic approaches that have been used to study AMPA and NMDA receptor subunits. These approaches have demonstrated that the GluA1 AMPA receptor subunit is required for activity-dependent trafficking and contributes to basal synaptic transmission, while the GluA2 subunit regulates Ca2+ permeability, homeostasis and trafficking to the synapse under basal conditions. In contrast, the GluN2A and GluN2B NMDA receptor subunits regulate synaptic AMPA receptor content, both during synaptic development and plasticity. Ongoing research in this field is focusing on the molecular interactions and mechanisms that control these functions. To accomplish this, molecular replacement techniques are being used, where native subunits are replaced with receptors containing targeted mutations. In this review, we discuss a single-cell molecular replacement approach which should arguably advance our physiological understanding of ionotropic glutamate receptor subunits, but is generally applicable to study of any neuronal protein.

AB - In the brain, fast, excitatory synaptic transmission occurs primarily through AMPA- and NMDA-type ionotropic glutamate receptors. These receptors are composed of subunit proteins that determine their biophysical properties and trafficking behaviour. Therefore, determining the function of these subunits and receptor subunit composition is essential for understanding the physiological properties of synaptic transmission. Here, we discuss and evaluate various genetic approaches that have been used to study AMPA and NMDA receptor subunits. These approaches have demonstrated that the GluA1 AMPA receptor subunit is required for activity-dependent trafficking and contributes to basal synaptic transmission, while the GluA2 subunit regulates Ca2+ permeability, homeostasis and trafficking to the synapse under basal conditions. In contrast, the GluN2A and GluN2B NMDA receptor subunits regulate synaptic AMPA receptor content, both during synaptic development and plasticity. Ongoing research in this field is focusing on the molecular interactions and mechanisms that control these functions. To accomplish this, molecular replacement techniques are being used, where native subunits are replaced with receptors containing targeted mutations. In this review, we discuss a single-cell molecular replacement approach which should arguably advance our physiological understanding of ionotropic glutamate receptor subunits, but is generally applicable to study of any neuronal protein.

UR - http://www.scopus.com/inward/record.url?scp=80052206400&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052206400&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2011.213033

DO - 10.1113/jphysiol.2011.213033

M3 - Article

C2 - 21768264

AN - SCOPUS:80052206400

VL - 589

SP - 4095

EP - 4101

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 17

ER -