Nucleoside transporters are divided into two families: the Na+-dependent solute carrier family 28 (SLC28) and the equilibrative solute carrier family 29 (SLC29). SLC28 family transporters (CNT1-3) display subtype-selective expression patterns; CNT1 is localized primarily to epithelial tissue whereas CNT2 and CNT3 have more widespread distributions.
SLC29 family transporters (ENT1-4) are glycosylated proteins, localized to the plasma and mitochondrial membranes. They are expressed in the heart, brain, mammary gland, erythrocytes and placenta, and also in fetal liver and spleen. They mediate nucleoside influx and efflux and exhibit highest affinity for adenosine.
CNT and ENT transporters play critical roles in nucleoside salvage pathways where they mediate the first step of nucleotide biosynthesis. In addition, these transporters work in concert to terminate adenosine signaling and are vital determinants in the response to a variety of cancer and antiviral treatments, as they modulate the entry of these nucleoside analogs into target tissues.
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