GluA2 | GluR2 | Glutamate Receptor Ionotropic, AMPA 2
The Glutamate receptor family has further been divided into ionotropic and metabotropic glutamate receptors.
The metabotropic glutamate receptor subfamily contains 8 members (mGluR1 - mGluR8)
The ionotropic glutamate receptors subfamily contains 16 members:
AMPA receptors: GluA1 (GluR1) - GluA4 (GluR4)
Kainate receptors: GluK1 (GluR5), GluK2 (GluR6), GluK3 (GluR7) , GluK4 (KA-1), GluK5 (KA-2)
NMDA receptors: GluN1 (NR1), GluN2A (NR2A), GluN2B (NR2B), GluN2C (NR2C), GluN2D (NR2D), GluN3A (NR3A), GluN3B (NR3B)
Regulation and Function:
Ionotropic glutamate receptors are ligand-gated nonselective cation channels that allow the flow of K+, Na+ and sometimes Ca2+ in response to glutamate binding. Metabotropic glutamate receptors belong to the subfamily C of G protein-coupled receptors. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.
GluA2: Background Information
GluA2 is a receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays a a major role in excitatory synaptic transmission. It is activated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), L-glutamate and kainate in the order AMPA (quisqualate) > glutamate > kainate. The GluA2 protein is encoded by the GRIA2 gene and four subunits are required to form a functional channel. Each subunit has 4 distinct domains: an extracellular amino acid terminal domain (ATD); the extracellular ligand binding domain (LBD); the transmembrane domain (TMD) with 3 transmembrane segments (M1, M3 and M4) and 1 cytoplasmic facing re-entrant loop (M2); and an intracellular carboxyterminal domain. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4, CACNG7 or CACNG8, the receptor shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate. The subunit encoded by the GRIA2 gene is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to render the channel impermeable to Ca2+. Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, (including the flip and flop isoforms that vary in their signal transduction properties), has been noted for this gene. AMPA receptors mediate fast excitatory synaptic transmission and play a role in hippocampal synaptic long-term potentiation and depression.
Brain, Pancreas: Bipotent Endocrine/Duct Progenitor cells, Spinal cord: Oligodendrocyte-like cells, Skeletal muskle: Limb Muscle Progenitor cells
Chemical synaptic transmission, ionotropic glutamate receptor signalling pathway
Status Epilepticus, Lateral Sclerosis, motor neuron disease, schizophrenia, amyotrophic lateral sclerosis 1
CACNG4, CACNG7, CACNG8, GRIP2, CSPG4, TARPs
MMP4, ATAD1, PICK1/PRKCABP, GRIA1, SYNDIG1, LRFN1, CACNG5, SNX27, OLFM2, AP4B1, AP4E1, AP4M1
Forms complex with:
GRIA1, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7, CACNG8; NSG1, GRIP1, STX12
Glutamate, AMPA, (S)-5-fluorowillardiine, ATPO, GYKI53655, GYKI53784, tezampanel, NBQX
Argiotoxin, LY404187, LY392098, cyclothiazide, aniracetam, CX516, CX546, IDRA-21, LY503430, piracetam, S18986
Patch Clamp: whole cell, ultrafast extracellular perfusion
A nomenclature for ligand-gated ion channels. Neuropharmacology 56:2-5, Collingridge G.L. et al. 2009
AMPA receptors have been implicated in depression, Parkinson's disease, Huntington's disease, ischemic stroke and neurodegenerative diseases such as dementia and Alzheimer's disease.