Concentrative nucleoside transporters (CNTs) in epithelia: from absorption to cell signaling

RESUMEN

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ABSTRACT

Concentrative and Equilibrative Nucleoside Transporter proteins (CNT andENT, respectively) are encoded by gene families SLC28 and SLC29. They mediatethe uptake of natural nucleosides and a variety of nucleoside-derived drugs, mostlyused in anticancer therapy. CNT and ENT proteins are mostly localized in the apicaland basolateral sides, respectively, in (re)absorptive epithelia. This anatomic distributiondetermines nucleoside and nucleoside-derived vectorial flux. CNT expression(particularly CNT2) is associated with differentiation and is also nutritionallyregulated in intestinal epithelia, whereas ENT protein amounts (mostly ENT1) areincreased when cells are exposed to proliferative stimuli such as EGF, TGF-á orwounding. Although all these features suggest a role for NT proteins in nucleosidesalvage and (re)absorption, recent data demonstrate that CNT2 might be underpurinergic control, in a manner that is dependent on energy metabolism. A physiologicallink between CNT2 function and intracellular metabolism is also supportedby the evidence that extracellular adenosine can activate the AMP-dependent kinase(AMPK), by a mechanism which relies upon adenosine transport and phosphorylation.Thus the complex pattern of NT isoform expression in mammalian cells can fulfillphysiological roles other than salvage