The 5-HT_2C receptor is a subtype of the 5-HT2 receptor that binds the endogenous

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 ...

serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, it is a

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

(GPCR) that is coupled to G_q/G₁₁ and mediates excitatory neurotransmission. ''HTR2C'' denotes the

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

encoding for the

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

, that in humans is located on the X chromosome. As males have one copy of the gene and females have one of the two copies of the gene repressed, polymorphisms at this receptor can affect the two sexes to differing extent.

Structure

At the cell surface the receptor exists as a homodimer. The crystal structure has been known since 2018.

Distribution

5-HT_2C receptors are located mainly in the

choroid plexus The choroid plexus, or plica choroidea, is a plexus of cells that arises from the tela choroidea in each of the ventricles of the brain. Regions of the choroid plexus produce and secrete most of the cerebrospinal fluid (CSF) of the central ...

, and in rats is also found in many other brain regions in high concentrations, including parts of the

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

, anterior olfactory nucleus,

substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...

, several

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

nuclei,

amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

, subthalamic nucleus and lateral habenula. 5-HT_2C receptors are also found on epithelial cells lining the ventricles.

Function

The 5-HT_2C receptor is one of the many binding sites for serotonin. Activation of this receptor by serotonin inhibits

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

release in certain areas of the brain. 5-HT_2C receptors are claimed to significantly regulate mood, anxiety, feeding, and reproductive behavior. 5-HT_2C receptors regulate dopamine release in the

striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

, and

, among others. Research indicates that some suicide victims have an abnormally high number of 5-HT_2C receptors in the prefrontal cortex. Agomelatine, which is a 5-HT_2C and 5-HT_2B

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.MT₁ and MT₂ agonist, is an effective

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 ...

. It has been called a norepinephrine-dopamine disinhibitor because antagonism of 5-HT_2C receptors by agomelatine results in an increase of dopamine and norepinephrine activity in the frontal cortex. Conversely, many SSRIs (but not fluoxetine, which is a 5-HT_2C antagonist) indirectly stimulate 5-HT_2C activity by increasing levels of serotonin in the

synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

. Many atypical antipsychotics block 5-HT_2C receptors, but their clinical use is limited by multiple undesirable actions on various

s and receptors . Fluoxetine acts as a direct 5-HT_2C antagonist in addition to inhibiting serotonin reuptake, however, the clinical significance of this action is variable. Several

tetracyclic antidepressant Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their tetracyclic chemical structure, containing four cyclic compound, rings of atoms, and are closely related to th ...

s, including

mirtazapine Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant, atypical tetracyclic antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks but ca ...

, are potent 5-HT_2C antagonists; this action may contribute to their efficacy. An overactivity of 5-HT_2C receptors may contribute to depressive and anxiety symptoms in a certain population of patients. Activation of 5-HT_2C by serotonin is responsible for many of the negative

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of SSRI and SNRI medications, such as sertraline, paroxetine, venlafaxine, and others. Some of the initial anxiety caused by SSRIs is due to excessive signalling at 5-HT_2C receptors. 5-HT_2C receptors exhibit constitutive activity ''in vivo'', and may retain the ability to influence neurotransmission in the absence of ligand occupancy. Thus, 5-HT_2C receptors do not require binding by a

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

(serotonin) in order to exhibit influence on neurotransmission. Inverse agonists may be required to fully extinguish 5-HT_2C constitutive activity, and may prove useful in the treatment of 5-HT_2C-mediated conditions in the absence of typical serotonin activity. In addition to the evidence for a role of 5-HT_2C receptor stimulation in depressive symptoms there also is evidence that activation of 5-HT_2C receptors may have beneficial effects upon certain aspects of depression, one group of researchers found that direct stimulation of 5-HT_2C receptors with a 5-HT_2C agonist reduced cognitive deficits in mice with a TPH2 loss-of-function mutation. 5-HT_2C receptors mediate the release and increase of extracellular dopamine in response to many drugs, including

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

, nicotine,

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

morphine Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

, and others. 5-HT_2C antagonism increases dopamine release in response to reinforcing drugs, and many dopaminergic stimuli. Feeding, social interaction, and sexual activity all release dopamine subject to inhibition of 5-HT_2C. Increased 5-HT_2C expression reduces dopamine release in both the presence and absence of stimuli. Conditions that increase

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

levels in the human body may have potential to raise 5-HT_2C gene expression in the brain. This could possibly comprise a link between viral infections and associated depression. Cytokine therapy has been shown to increase 5-HT_2C gene expression, resulting in increased activity of 5-HT_2C receptors in the brain .

Endocrinology

Serotonin is involved in basal and stress-induced regulation of

and

pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...

hormones such as

prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...

, adrenocorticotropic hormone ( ACTH), vasopressin and

oxytocin Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include Human bonding, ...

, mainly via actions of receptor subtypes 5-HT_2A and 5-HT_2C. Therefore, the 5-HT_2C receptor is a significant modulator of the hypothalamic–pituitary–adrenal axis ( HPA axis). The HPA axis is the main controller of acute sympathetic stress responses related to fight-or-flight response. Prolonged activation and disturbances of the HPA axis contribute to depressive and anxiety symptoms seen in many psychopathological conditions. Stimulation of 5-HT_2C receptors leads to increase of corticotropin releasing hormone ( CRH) and vasopressin mRNA in the paraventricular nucleus and proopiomelanocortin in the anterior pituitary lobe. In rats, restraint stress (which can produce depressive symptoms if being chronic) induces secretion of prolactin, ACTH, vasopressin and oxytocin which is partially mediated via 5-HT_2C receptor. Responses during such conditions as dehydration or haemorrhage causes the release of oxytocin via serotonergic response that is partly mediated by 5-HT_2C. In addition, peripheral release of vasopressin involves serotonergic response which is partially mediated via 5-HT_2C. Expression of the 5-HT_2C receptor in the CNS is modulated by female sex hormones estradiol and

progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

. Combination of the hormones decrease the receptor concentration in the ventral

in rats and could thus affect mood.

Genetics

Many human polymorphisms have been identified influencing the expression of 5-HT_2C. Significant correlations are suggested, specifically in relation to psychiatric disorders such as depression, OCD, and anxiety-related conditions. Polymorphisms also correlate with susceptibility to a number of conditions including substance use disorders and

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

. There are indications that the alternative splicing of the 5-HT_2C receptor is regulated by a snoRNA called SNORD115, the deletion of which is associated with

Prader–Willi syndrome Prader–Willi syndrome (PWS) is a rare genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include hypotonia, weak muscles, poor feeding, and slow development. Beginning in childhood, those ...

. As the human gene is located in the X chromosome, males have only one copy of the gene whereas women have two, meaning that mutations in the gene affect the phenotype of men even when the allele would be recessive in nature. As women have two copies of the gene, but only one allele is expressed in each cell, they are a mosaic for polymorphisms, meaning that one genetic variant may be prevalent in one tissue and another variant will be prevalent in a different tissue (as with all other x-linked genetic variations).

Ligands

Agonists

* A-372,159 * AL-38022A * Bexicaserin * BMB-101 * CP-809,101 * CPD-1 * Fenfluramine * Lisuride * Lorcaserin * Mesulergine * MK-212 * Naphthylisopropylamine * Norfenfluramine * NU-1223 * Org 12,962 * ORG-37,684 * Oxaflozane * PF-04479745 * PNU-22394 * PNU-181731 * Psychedelics ** Lysergamides ( LSD, etc.) ** Phenethylamines ( 2C-B, DOI, DOM,

Mescaline Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...

, etc.) ** Piperazines ( mCPP, TFMPP, etc.) ** Tryptamines ( 5-MeO-DMT, Bufotenin, DMT, Psilocin, etc.) * Ro60-0175 * Vabicaserin * WAY-629 * WAY-161,503 * WAY-163,909 * WAY-261240 * YM-348 * CP-132,484 also 5HT2a agonist.

Partial agonists

* Aripiprazole * Venlafaxine

Antagonists

* Agomelatine * CEPC * Clozapine * Eltoprazine * Etoperidone * Flibanserin * Fluoxetine * FR-260,010 * Tedatioxetine * Methysergide *

Mirtazapine Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant, atypical tetracyclic antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks but ca ...

* Nefazodone * Norfluoxetine * O-Desmethyltramadol * Olanzapine * Promethazine * RS-102,221 * SB-200,646 * SB-221,284 * SB-228,357 * SB-242,084 * SDZ SER-082 * Tramadol * Trazodone

Peripherally selective antagonists

* BW-501C67 * Sarpogrelate * Xylamidine

Inverse agonists

* Antidepressants ** Tricyclics ( Amitriptyline and Nortriptyline most notably) ** Tetracyclics (

, Mianserin, Amoxapine, etc.) *

Antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...

s ( Cyproheptadine, Hydroxyzine, Latrepirdine, etc.) *

Antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

s ** Typicals (

Chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...

, Fluphenazine, Loxapine, Thioridazine, etc.) ** Atypicals ( Clozapine, Olanzapine,

Risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...

, Ziprasidone, etc.) * Cinanserin * Deramciclane * Ketanserin * LY-53,857 * Metergoline * Methiothepin * Pizotifen * Ritanserin * S-32212 * SB-206,553 * SB-228,357 * SB-243,213 * SB-242,084

Positive allosteric modulators

Exogenous PAMs of the serotonin 5-HT_2C receptor include: * CYD-1-79 * CTW-0415 * VA012

Interactions

The 5-HT_2C receptor has been shown to interact with MPDZ.

RNA editing

5HT2CR pre-mRNA can be the subject of RNA editing. It is the only serotonin receptor as well as the only member of the large family of 7 transmembrane receptors (7TMRs) known to be edited. Different levels of editing result in a variety of effects on receptor function.

Type

The type of RNA editing that occurs in the

pre-mRNA A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by Transcription (genetics), transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcript ...

of the 5HT2CR is Adenosine to Inosine (A to I) editing. A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1–3 with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS). ADARs bind interact directly with the dsRNA substrate via their double stranded RNA binding domains. If an editing site occurs within a coding sequence, it can result in a codon change. This can lead to translation of a protein isoform due to a change in its primary protein structure. Therefore, editing can also alter protein function. A to I editing occurs in a non coding RNA sequences such as

introns An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of ...

, untranslated regions (UTRs), LINEs, SINEs ( especially Alu repeats) The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus amongst others.

Location

Editing occurs in 5 different closely located sites within exon 5, which corresponds to the second intracellular loop of the final protein. The sites are known as A, B, C′ (previously called E), C and D, and are predicted to occur within amino acid positions 156, 158 and 160. Several codon changes can occur due to A-to-I editing at these sites. Thirty-two different mRNA variants can occur leading to 24 different protein isoforms. #An Isoleucine to Valine (I/V) at amino acid position 157,161. #An Isoleucine to a Methionine(I/M) at amino acid position 157 #An Aspartate to a Serine (N/S)at 159 #An Aspartate to Asparagine(N/D) at 159 #An Asparagine to a Glycine(N/G) at 159. These codon changes which can occur due to A to I editing at these sites can lead to a maximum of 32 different mRNA variants leading to 24 different protein isoforms. The number of protein isoforms is less than 32 since some amino acids are encoded by more than one codon. Another editing site, site F has also been located in the exon complementary sequence (ECS) of intron 5. The ECS required for formation of double stranded RNA structure is found within intron 5.

Conservation

RNA editing of this receptor occurs at 4 locations in the rat. Editing also occurs in the mouse. The initial demonstration of RNA editing in rat. The predominant isoform in rat brain is VNV which differs from the most common type found in humans. The editing complementary sequence is known to be conserved across Mammalia.

Regulation

The 5-HT_2c receptor is the only serotonin receptor edited despite its close sequence similarities to other family members. 5HT2CR is different due to possessing an imperfect inverted repeat at the end of exon 5 and the beginning of intron 5 allowing formation of an RNA duplex producing the dsRNA required by ADARs for editing. Disruption of this inverted repeat was demonstrated to cease all editing. The different 5HT2CR mRNA isoforms are expressed differently throughout the brain, yet not all of the 24 have been detected perhaps due to tissue specific expression or low frequency editing of a particular type. Those isoforms that are not expressed at all or at a very low frequency are linked by being edited only at site C' and/or site B but not at site A. Some examples of differences in frequency of editing and site edited in different parts of the human brain of 5HT2CR include low frequency of editing in cerebellum and nearly all editing is at site D while in the hippocampus editing frequency is higher with site A being the main editing site. Site C' is only found edited in the thalamus. The most common isoform in human brain is the VSV isoform. Mice knock out and other studies have been used to determine which ADAR enzyme are involved in editing. Editing at A and B sites has been demonstrated to be due to ADAR1 editing. Also since ADAR1 expression is increased in response to the presence of interferon α, it was also observed that editing at A and B sites was also increased because of this. C' and D sites require ADAR2 and editing is decreased by the presence of ADAR1 with editing of C' site only observed in ADAR1 double knock out mice. The C site has been shown to be mainly edited by ADAR2 but in presence of upregulated expression of ADAR1, there was an increase in editing of this site and the enzymes presence can also result in limited editing in ADAR 2 knock out mice. This demonstrates that there must be some form interaction between the two A to I editing enzymes. Also such interactions and tissue specific expression of ADARs interaction may explain the variety in editing patterns in different regions of the brain.

Consequences

Second, the editing pattern controls the amount of the 5-HT2CR mRNA that leads to the expression of full-length protein through the modulation of alternative splice site selection 76,77. Among three alternative splice donor sites (GU1 to GU3; Fig. 4C), GU2 is the only site that forms the mature mRNA to produce the functional, full-length 5-HT2CR protein. Unedited pre-mRNAs tend to be spliced at the GU1 site, resulting in the truncated, non-functional protein if translated 76,77. However, most pre-mRNAs edited at more than one position are spliced at GU2 77. Thus, when editing is inefficient, increased splicing at GU1 may act as a control mechanism to decrease biosynthesis of the 5-HT2CR-INI and thereby limit serotonin response. Third, RNA editing controls the ultimate physiological output of constitutively active receptors by affecting the cell surface expression of the 5-HT2CR. The 5-HT2CR-VGV, which displays the lowest level of constitutive activity, is fully expressed at the cell surface under basal conditions and is rapidly internalized in the presence of agonist 78; additionally, in vitro, LSD shows negligible activity with this isoform. In contrast, the 5-HT2CR-INI is constitutively internalized and accumulates in endosomes 78. Structure As mentioned editing results in several codon changes. The editing sites are found in the second intracellular domain of the protein which is also the receptors G protein coupling domain. Therefore, editing of these sites can affect the affinity of the receptor for G protein binding. Function Editing results in reduced affinity for specific G proteins which in turn affects internal signalling via second messengers (Phospholipase C signalling system). The fully edited isoform, VGV, considerably reduces 5-HT potency, G-protein coupling and agonist binding, compared to the unedited protein isoform, INI. 72–76. Most evidence for the effect of editing on function comes from downstream measurements of receptor activity, radio ligand binding and functional studies. Inhibitory effects are linked to the extent of editing. Those isoforms with a higher level of editing require higher levels of serotonin to activate the phospholipase c pathway. Unedited INI form has a greater tendency to isomerise to an active form which can more easily interact with G proteins. This indicates that RNA editing here may be a mechanism for regulating neuronal excitability by stabilising receptor signalling. Editing is also thought to function in cell surface expression of the receptor subtype. The fully edited VGV, which has the lowest level of constitutive activity, is fully expressed at the cell surface while the non-edited INI is internalised and accumulates in endosome. Editing is also thought to influence splicing. Three different spliced isoforms of the receptor exist. Editing regulates the amount of 5HT2CR mRNA which leads to translation of the full length protein selection of alternative splice sites. t76,77. These splice sites are termed Gu1, Gu2, GU3. Only GU2 site splicing results in translation of the full length receptor while editing at GU1 is known to result in translation of a truncated protein. This is thought to be a regulatory mechanism to decrease the amount of unedited isoform INI to limit serotonin response when editing is inefficient. Most of the pre-mRNAs which are edited are spliced at the GU2 site. Dysregulation Serotonin family of receptors are often linked to pathology of several human mental conditions such as Schizophrenia, anxiety, Bipolar disorder and major depression. There have been several experimental investigations into the effects of alternative editing patterns of the 5HT2CR and these conditions with a wide variability in results especially those relating to schizophrenia. Some studies have noted that there is an increase in RNA editing at site A in depressed suicide victims. E site editing was observed to be increased in individuals with major depression. In rat models this increase is also observed and can be reversed with fluoxetine with some suggestion that E site editing maybe linked to major depression.

References

External links

* *