SLC6 neurotransmitter transporters: structure, function, and regulation.

Publisher: American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 0421737 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-0081 (Electronic) Linking ISSN: 00316997 NLM ISO Abbreviation: Pharmacol Rev Subsets: MEDLINE

Publication: Bethesda, Md : American Society for Pharmacology and Experimental Therapeutics
Original Publication: Baltimore, Williams & Wilkins.

Amino Acid Transport Systems, Neutral/*chemistry ; Amino Acid Transport Systems, Neutral/*metabolism ; Nerve Tissue Proteins/*chemistry ; Nerve Tissue Proteins/*metabolism ; Plasma Membrane Neurotransmitter Transport Proteins/*chemistry ; Plasma Membrane Neurotransmitter Transport Proteins/*metabolism; Amino Acid Transport Systems, Neutral/agonists ; Amino Acid Transport Systems, Neutral/antagonists & inhibitors ; Animals ; Humans ; Ligands ; Membrane Microdomains/metabolism ; Molecular Targeted Therapy ; Nerve Tissue Proteins/agonists ; Nerve Tissue Proteins/antagonists & inhibitors ; Neurons/drug effects ; Neurons/metabolism ; Organ Specificity ; Plasma Membrane Neurotransmitter Transport Proteins/agonists ; Plasma Membrane Neurotransmitter Transport Proteins/antagonists & inhibitors ; Protein Isoforms/agonists ; Protein Isoforms/antagonists & inhibitors ; Protein Isoforms/chemistry ; Protein Isoforms/metabolism ; Protein Processing, Post-Translational ; Protein Transport ; Synaptic Transmission/drug effects

The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na(+)/Cl(-)-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. The SLC6 NTTs are widely expressed in the mammalian brain and play an essential role in regulating neurotransmitter signaling and homeostasis by mediating uptake of released neurotransmitters from the extracellular space into neurons and glial cells. The transporters are targets for a wide range of therapeutic drugs used in treatment of psychiatric diseases, including major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy. Furthermore, psychostimulants such as cocaine and amphetamines have the SLC6 NTTs as primary targets. Beginning with the determination of a high-resolution structure of a prokaryotic homolog of the mammalian SLC6 transporters in 2005, the understanding of the molecular structure, function, and pharmacology of these proteins has advanced rapidly. Furthermore, intensive efforts have been directed toward understanding the molecular and cellular mechanisms involved in regulation of the activity of this important class of transporters, leading to new methodological developments and important insights. This review provides an update of these advances and their implications for the current understanding of the SLC6 NTTs.

0 (Amino Acid Transport Systems, Neutral)
0 (Ligands)
0 (Nerve Tissue Proteins)
0 (Plasma Membrane Neurotransmitter Transport Proteins)
0 (Protein Isoforms)

Date Created: 20110715 Date Completed: 20111125 Latest Revision: 20220318

20221213

10.1124/pr.108.000869

21752877