Solute Carrier Family 6

The human solute carrier family 6 (SLC6) is composed of transporters for neurotransmitters, proteinogenic amino acids, betaine, taurine, and creatine. Based on sequence similarity, these transporters are divided into four branches, namely the GABA transporter branch, the monoamine transporter branch, and the amino acid transporter branch (I) and (II). The GABA transporters include SLC6A1, SLC6A8, SLC6A6, SLC6A11, SLC6A12, SLC6A13. The monoamine transporters contain SLC6A2-4. The amino acid transporter branch (I) contains SLC6A5, SLC6A7, SLC6A9, SLC6A14, while the amino acid transporter branch (II) contains SLC6A15, SLC6A16, SLC6A17, SLC6A19, SLC6A20. These four branches of transporters have different substrate preferences but the substrate specificity if overlapping. Members of this family play critical roles in neurotransmission, cellular and whole body homeostasis. Studies have revealed the role of members of the SLC6 family in a variety of disease states, such as inherited Mendelian disorders and more complex multifactorial diseases.

The pharmacology of these members has been developed to different extents. Currently, a number of inhibitors and synthetic substrates have been developed targeting monoamine transporters, whereas the pharmacology of GABA and glycine transporters are less well-developed. Pharmacological inhibition of the neurotransmitter transporters in this family is an important strategy in the management of neurological and psychiatric disorders. However, the remaining transporters are largely unexplored.

Herein, we give an introduction to the following members of human solute carrier family 6, regarding the substrate specificity, transport mechanisms, pharmacology development, and recent research advance.

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