SLC - Solute Carrier Superfamily
Solute carriers (SLC) are a group of membrane transport proteins, comprising over 300 members, most of which are located in cell membranes. Their main function is to facilitate the transport of a wide variety of substrates across biological membranes, including the uptake of small molecules into cells.
The SLC superfamily of solute carriers is the second largest family of membrane proteins after G protein-coupled receptors. Within the superfamily, there is a great diversity of structure, but they are united by their function. Over 50 families have been identified based on sequence similarities, but many of them overlap in terms of the solutes that they carry. Two families (SLC3 and SLC7) only generate functional transporters as heteromeric partners, where one partner is a single trans-membrane domain protein. Functionally, members can be divided into those dependent on gradients of ions (particularly sodium, chloride or protons), exchange of solutes or simple equilibrative gating. For many members, the stoichiometry of transport is not yet established. One family of transporters also possess enzymatic activity (SLC27), while many members function as ion channels (e.g. SLC1A7/EAAT5), which increases the complexity of function of the SLC superfamily.
Membrane transporters are widely expressed throughout the body, in the epithelia of major organs, such as the liver, intestine, kidney, and organs with barrier functions, such as the brain, testes and placenta. Different transporters are localised to the plasma membrane, as well as to the membranes of various subcellular organelles. This maintains cellular homeostasis due to the regulated delivery of required substrates. SLC transporters therefore have important roles in physiological processes ranging from the cellular uptake of nutrients to the absorption of drugs and other xenobiotics.
ATP-binding cassette (ABC) Superfamily
Traditionally, a greater emphasis has been placed on the development of drugs targeted at the other transporter superfamily, the ATP-binding cassette (ABC) superfamily. Fewer therapeutic drugs have been developed to exploit SLC family targets but interest in this diverse family of proteins is now growing. Several classes of marketed drugs now target well-known SLC transporters, such as neurotransmitter transporters, and human genetic studies have provided powerful insight into the roles of more-recently characterised SLC transporters in both rare and common diseases, indicating a wealth of new therapeutic opportunities.