Anales RANF

S5-02 ROLE OF CONCENTRATIVE NUCLEOSIDE TRANSPORTERS (CNT) IN ADENOSINE TRANSPORT AND METABOLISM S. Pérez-Torras University of Barcelona, Institute of Biomedicine (IBUB), Barcelona, Spain. Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (IRP-HSJD), Esplugues de Llobregat, Spain. National Biomedical Research Institute on Liver and Gastrointestinal Diseases (CIBER EHD), Madrid, Spain. Extracellular adenosine concentrations are regulated by a panel of membrane transporters which, in most cases mediate its uptake into cells. Adenosine transporters belong to two gene families, SLC28 and SLC29 , encoding Concentrative and Equilibrative Nucleoside Transporter proteins (CNTS and ENTs, respectively). Both families share common features such as substrate selectivity and often tissue localization. This apparent biological redundancy may anticipate some different roles for hCNTs and hENTs in cell physiology. Thus, hENTs may have a major role in maintaining nucleoside homeostasis, whereas hCNTs could contribute to nucleoside sensing and signal transduction. Among all the nucleoside transporters hENT1 has often been identified as a major player in purinergic signalling. However, the role of CNTs cannot be disdained, specifically hCNT2 and hCNT3 that should be the best candidates for efficient removal of adenosine considering their apparent high affinity for this nucleoside and their concentrative capacity. Moreover, solid evidences exist demonstrating that both transporters are under purinergic regulation albeit to some extent they seem to exert their functions in different tissues. Nevertheless, the role of hCNTs in purinergic signalling seems not to be only restricted to their mere uptake ability. In this regard, our results point to a more complex network in which protein interactions would play a major role in the coordinate regulation of nucleotide metabolism. Using proteomic approaches, we have identified putative hCNT3 protein partners that suggest that hCNT3 would be part of a cellular sensor of purine bioavailability, likely to include nucleotide metabolic enzymes regulating nucleotide de novo and salvage pathways.