title: Human genetics and pharmacology of neurotransmitter transporters.
abstract: Biogenic amine neurotransmitters are released from nerve terminals and activate pre- and postsynaptic receptors. Released neurotransmitters are sequestered by transporters into presynaptic neurons, a major mode of their inactivation in the brain. Genetic studies of human biogenic amine transporter genes, including the dopamine transporter (hDAT; SLC6A3), the serotonin transporter (hSERT; SLC6A4), and the norepinephrine transporter (hNET; SLC6A2) have provided insight into how genomic variations in these transporter genes influence pharmacology and brain physiology. Genetic variants can influence transporter function by various mechanisms, including substrate affinities, transport velocity, transporter expression levels (density), extracellular membrane expression, trafficking and turnover, and neurotransmitter release. It is increasingly apparent that genetic variants of monoamine transporters also contribute to individual differences in behavior and neuropsychiatric disorders. This chapter summarizes current knowledge of transporters with a focus on genomic variations, expression variations, pharmacology of protein variants, and known association with human diseases.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Division of Neurochemistry, New England Primate Research Center, 1 Pine Hill Drive, Southborough, MA 01772-9102, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
authors.forename: B K
authors.initials: BK
authors.lastname: Madras
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011605:Psychoses, Substance-Induced / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins