SEROTONIN TRANSPORTER

The 'serotonin transporter' is a monoamine transporter protein.

Contents

Function

Pharmacology

Genetics

Noncoding polymorphisms

References

Notes

Other

Function

It reuptakes serotonin in synaptic cleft and terminate its function. It allows neurons, platelets, and other cells to accumulate the chemical neurotransmitter serotonin, which affects emotions and drives.
Neurons communicate by using chemical messages like serotonin between cells. The transporter protein, by recycling serotonin, regulates its concentration in a gap, or synapse, and thus its effects on a receiving neuron’s receptor.
Medical studies have shown that changes in serotonin transporter metabolism appear to be associated with many different phenomena, including alcoholism, clinical depression, obsessive-compulsive disorder (OCD), romantic love and hypertension.

Pharmacology

SERT spans the plasma membrane 12 times. It belongs to NE, DA, SERT monoamine transporter family. Transporters are important sites for agents that treat psychiatric disorders. Drugs that reduce the binding of serotonin to transporters (selective serotonin reuptake inhibitors, or SSRIs) are used to treat mental disorders. About half of patients with OCD are treated with SSRIs. Fluoxetine is an example of a selective serotonin reuptake inhibitor.

Genetics

The gene that encodes the serotonin transporter is called ''solute carrier family 6 (neurotransmitter transporter, serotonin), member 4'' (SLC6A4).
There are a number of other names for this gene, e.g., in humans it may be referred to as ''hSERT''. Other aliases are 5-HTT, 5HTT, HTT, OCD1 and SERT according to GeneCards.
Researchers have found an uncommon mutation in SLC6A4, in some unrelated families with OCD, that leads to faulty transporter function and regulation. A second variant in the same gene of some patients with this mutation suggests a genetic "double hit", resulting in greater biochemical effects and more severe symptoms.

Noncoding polymorphisms

The promotor region of the SLC6A4 gene contains a polymorphism with "short" and "long" repeats in a region: 5-HTT-linked polymorphic region (5-HTTLPR).
The short variation leads to less transcription of SLC6A4, and it has been found that it can partly account for anxiety-related personality traits^[1].
This polymorphism has been extensively investigated in over 300 scientific studies (as of 2006)^[2]
Another noncoding polymorphism is a VNTR in the second intron (STin2). It is found with three alleles: 9, 10 and 12 repeats.

References

Notes

1. Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region, Klaus-Peter Lesch, Dietmar Bengel, Armin Heils, Sue Z. Sabol, Benjamin D. Greenberg, Susanne Petri, Jonathan Benjamin, Clemens R. Müller, Dean H. Hamer, Dennis L. Murphy, , , Science, 1996
2.

Other

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★ NIH press release: Serotonin Transporter Gene Shown to Influence College Drinking Habits

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