Emerging Roles of Transporters

Transporter-related proteins encompass about 10% of human genes, highlighting their biological relevance. They include the SoLute Carrier (SLC) transporters superfamily, ATP-binding cassette (ABC) transporters, channels and pumps. SLC and ABC transporter functions have been studied for decades. In fact, membrane transporters have been often considered as mere translocators of a variety of substrates likely to contribute to nutrient and ion supply for cells. Knowledge on transporter selectivity and specificity is broad but the biological impact of transporters on cell function beyond their mere role as suppliers of substrates is less well known. However, in the last years, novel roles are emerging for a growing number of these proteins. This latter evidence has led to the concept of selected transporters behaving as transceptors. This concept deals with the idea that besides the translocation function of substrates either into or out of cells, transporters can also be implicated in cell signaling processes. In some cases, this may even be independent of their translocation properties, although in many other not. Nutrient transceptors have been identified throughout the eukaryotes such as yeast, animals and plants. Most membrane transceptors share the ability to sense the availability of their substrates activating cell signaling cascades when needed. Those transceptors include hitherto transporters of a wide variety of substrates like amino acid, sulfur, nitrate and glucose. Furthermore, transporter biochemistry is now revealing emerging roles for these membrane proteins and selected transporter proteins are being implicated in important pathological events such as oncogenesis. This has been reported for monocarboxylate, amino acid, iodide, and nucleoside transporters among others. Thus, there are excellent examples of transporters playing key roles in cell function beyond the mere supply of nutrients and many other have to come strengthen the relevance of transceptor biological role. This change of paradigm in transporter biology opens new possibilities in pharmacology because no matter whether some of these transporters are drug translocators or not, they themselves and their interactome may become druggable targets in the future.