GRIA3

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]

Full Name

Glutamate Ionotropic Receptor AMPA Type Subunit 3

Function

Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. 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 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.

Biological Process

Glutamate receptor signaling pathway Source: ProtInc

Cellular Location

Cell membrane; Postsynaptic cell membrane. Interaction with CNIH2 and CNIH3 promotes cell surface expression.

Involvement in disease

Mental retardation, X-linked 94 (MRX94):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. MRX94 patients have moderate mental retardation. Other variable features are macrocephaly, seizures, myoclonic jerks, autistic behavior, asthenic body habitus, distal muscle weakness and hyporeflexia.

Topology

Extracellular: 29-552
Helical: 553-573
Cytoplasmic: 574-602
Helical: 603-618
Extracellular: 619-621
Helical: 622-627
Cytoplasmic: 628-648
Helical: 649-823
Extracellular: 824-844
Helical: 845-894

PTM

Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-621 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-847 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity).