GRIK4 (''glutamate receptor, ionotropic, kainate 4'') is a

kainate receptor Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a dr ...

subtype belonging to the family of

ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as sodium, Na+, potassium, K+, calcium, Ca2+, and/or chloride, Cl− to ...

s which is encoded by the gene.

Function

This gene encodes a protein that belongs to the glutamate-gated ionic channel family.

Glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

functions as the major excitatory

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members.

Clinical significance

single nucleotide polymorphism In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...

( rs1954787) in the GRIK4 gene has shown a treatment-response-association with

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

treatment. Variation in GRIK4 have been associated with both increased and decreased risk of

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

. A possible mechanism for this observation is that the sequence variation influences secondary structures in the 3' UTR. Interfering with GRIK4/KA1 function with a specific anti-KA1 antibody protects against kainate-induced neuronal cell death. A test of that gene can be made in order to know if a depressed patient will respond to the

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by ...

citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and soci ...

Evolutionary significance

The GRIK4 gene displayed significantly higher rates of evolution in primates than in rodents and especially in the lineage leading from primates to humans. Furthermore, the GRIK4 gene is implicated in the development of the nervous system. Hence evolution of the GRIK4 gene is thought to have played a role in the dramatic increases in size and complexity of the brain that occurred during evolutionary history leading to humans.

References

External links

* * {{Ligand-gated ion channels Ionotropic glutamate receptors Biology of bipolar disorder