RT Journal Article
SR Electronic
T1 Role of the Transporter Regulator Protein (RS1) in the Modulation of Concentrative Nucleoside Transporters (CNT) in epithelia
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.111.076992
DO 10.1124/mol.111.076992
A1 Ekaitz Errasti-Murugarren
A1 Paula Fernandez-Calotti
A1 Mayke Veyhl-Wichmann
A1 Maximilian Diepold
A1 Itziar Pinilla-Macua
A1 Sandra Perez-Torras
A1 Helmut Kipp
A1 Hermann Koepsell
A1 Marcal Pastor-Anglada
YR 2012
UL http://molpharm.aspetjournals.org/content/early/2012/04/09/mol.111.076992.abstract
AB Solute Carrier 28 (SLC28) genes encode three plasma membrane transporter proteins, hCNT1, hCNT2, and hCNT3, all implicated in the uptake of natural nucleosides and a variety of nucleoside analogues used in the chemotherapy of cancer, viral and inflammatory diseases. Mechanisms determining their trafficking towards the plasma membrane are not well known, although this might eventually become a target for therapeutic intervention. The transporter regulator RS1, initially identified as a short-term post-transcriptional regulator of the high affinity Na+-coupled glucose transporter SGLT1, has been evaluated in this study as a candidate to co-ordinately regulate membrane insertion of hCNT-type proteins. By combining studies in mammalian cells, in Xenopus laevis oocytes and the analysis of the RS1 null mice, evidence is provided that RS1 down-regulates the localization and activity at the plasma membrane of the three members of this protein family, CNT1, CNT2, and CNT3, thus providing the biochemical basis for a coordinate regulation of nucleoside uptake ability in epithelia and, highly likely, in other RS1 expressing cell types.