Glycine receptor
Encyclopedia
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
for the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory receptors in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brain stem.
The receptor can be activated by a range of simple amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s including glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
, β-alanine
Beta-alanine
β-Alanine is a naturally occurring beta amino acid, which are amino acids in which the amino group is at the β-position from the carboxylate group . The IUPAC name for β-alanine would be 3-aminopropanoic acid...
and taurine, and can be selectively blocked by the high-affinity competitive antagonist strychnine
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
. Caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
has recently been found to also be a competitive antagonist.
Arrangement of subunits
Strychnine-sensitive glycine receptors are members of a family of Ligand-gated ion channelLigand-gated ion channel
Ligand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...
s. Receptors of this family are arranged as five subunit
Protein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
s surrounding a central pore, with each subunit composed of four α helical
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
transmembrane
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
segments.
There are presently four known isoforms of the α-subunit (α1-4) of GlyR that are essential to bind ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
s and a single β-subunit .
The adult form of the GlyR is the heteromeric α1β receptor, which is believed to have a stoichiometry (proportion) of three α1 subunits and two β subunits
or four α1 subunits and one β subunit. The α-subunits are also able to form functional homo-pentamer
Pentamer
A pentamer is a thing composed out of five sub-units.In chemistry, it applies to molecules made of five monomers.In biochemistry, it applies to macromolecules, in particular to pentameric proteins, made of five proteic sub-units....
ic receptors in heterologous expression systems in African clawed frog's
African clawed frog
The African clawed frog is a species of South African aquatic frog of the genus Xenopus. Its name is derived from the three short claws on each hind foot, which it uses to tear apart its food...
oocyte
Oocyte
An oocyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell which undergoes a mitotic...
s or mammalian cell lines, and the α1 homomeric receptor is essential for studies of channel pharmacokinetics
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...
and pharmacodynamics
Pharmacodynamics
Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect...
.
Glycine receptors in diseases
Disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions results in the rare neurological disorder, hyperekplexiaHyperekplexia
Hyperekplexia is a neurologic disorder classically characterised by pronounced startle responses to tactile or acoustic stimuli and hypertonia. The hypertonia may be predominantly truncal, attenuated during sleep and less prominent after a year of age...
. The disorder is characterized by an exaggerated response to unexpected stimuli which is followed by a temporary but complete muscular rigidity often resulting in an unprotected fall. Chronic injuries as a result of the falls are symptomatic of the disorder. A mutation in GLRA1 is responsible for some cases of stiff person syndrome
Stiff person syndrome
Stiff person syndrome is a rare neurologic disorder of unknown etiology characterized by progressive rigidity and stiffness, primarily of the axial musculature, that is superimposed by spasms, resulting in postural deformities...
.
Research
Quantum dots have been used to track the diffusion of glycine receptors into the synapseSynapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
of neurons.
Formation of the mature GlyR complex at the post-synaptic membrane was found to be reliant on presence of a protein called gephyrin
Gephyrin
Gephyrin is a protein that is a component of the postsynaptic protein network of inhibitory synapses. Positive antibody staining for gephyrin at a synapse is consistent with the presence of glycine and/or GABA-A receptors. Gephyrin displaces GABA receptors from the GABARAP/P130 complex, then brings...
, via knockout studies in mice.
Agonists
- AlanineAlanineAlanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
- CycloserineCycloserineCycloserine is an antibiotic effective against Mycobacterium tuberculosis. For the treatment of tuberculosis, it is classified as a second line drug, i.e...
- DimethylglycineDimethylglycineDimethylglycine is a derivative of the amino acid glycine with the structural formula 2NCH2COOH. It can be found in beans and liver. It can be formed from trimethylglycine upon the loss of one of its methyl groups...
- GlycineGlycineGlycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
- HypotaurineHypotaurineHypotaurine is a sulfinic acid that is an intermediate in the biosynthesis of taurine. Like taurine, it also acts as an endogenous neurotransmitter via action on the glycine receptors.- References :...
- Methylglycine (Sarcosine)
- MilacemideMilacemideMilacemide is a MAO-B inhibitor and glycine prodrug. It has been studied for its effects on human memory and as a potential treatment for the symptoms of Alzheimer's disease. Early clinical trials, however, showed no positive results....
- SerineSerineSerine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
- Taurine
- TrimethylglycineTrimethylglycineTrimethylglycine is an organic compound that occurs in plants as either glycine betaine or a choline-containing glycine betaine compound. Trimethylglycine was the first betaine discovered by science; originally it was simply called betaine because, in the 19th century, it was discovered in sugar...
(Betaine)
Antagonists
- BicucullineBicucullineBicuculline is a light-sensitive competitive antagonist of GABAA receptors. It was originally identified in 1932 in plant alkaloid extracts and has been isolated from Dicentra cucullaria, Adlumia fungosa, Fumariaceae, and several Corydalis species. Since it blocks the inhibitory action of GABA...
- BrucineBrucineBrucine is a bitter alkaloid closely related to strychnine. It occurs in several plant species, the most well known being the Strychnos nux-vomica tree, found in South-East Asia.While brucine is related to strychnine, it is not as poisonous...
- CaffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
- PicrotoxinPicrotoxinPicrotoxin, also known as cocculin, is a poisonous crystalline plant compound, first isolated by Pierre Boullay in 1812. The name "picrotoxin" is a combination of the Greek words "picros" and "toxicon" ....
- StrychnineStrychnineStrychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
- TutinTutin (toxin)Tutin is a poisonous plant derivative found in the New Zealand tutu plant . It acts as a potent antagonist of the glycine receptor, and has powerful convulsant effects...