Different N-terminal motifs determine plasma membrane targeting of the human concentrative nucleoside transporter 3 in polarized and nonpolarized cells

Molecular Pharmacology
Ekaitz Errasti-MurugarrenMarçal Pastor-Anglada

Abstract

Human concentrative nucleoside transporter 3 (hCNT3) is a broad-selectivity, high-affinity protein implicated in the uptake of most nucleoside-derived anticancer and antiviral drugs. Regulated trafficking of hCNT3 has been recently postulated as a suitable way to improve nucleoside-based therapies. Moreover, the recent identification of a putative novel hCNT3-type transporter lacking the first 69 amino acids and retained at the endoplasmic reticulum anticipated that the N terminus of hCNT3 contains critical motifs implicated in trafficking. In the current study, we have addressed this issue by using deletions and site-directed mutagenesis and plasma membrane expression and nucleoside uptake kinetic analysis. Data reveal that 1) a segment between amino acids 50 and 62 contains plasma membrane-sorting determinants in nonpolarized cells; 2) in particular, the Val(57)-Thr(58)-Val(59) tripeptide seems to be the core of the export signal, whereas acidic motifs upstream and downstream of it seem to be important for the kinetics of the process; and 3) in polarized epithelia, the β-turn-forming motif (17)VGFQ(20) is necessary for proper apical expression of the protein.

References

Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B del SantoM Pastor-Anglada
May 21, 1999·The Journal of Biological Chemistry·N NishimuraW E Balch
Nov 24, 1999·The Journal of Clinical Investigation·B D MoyerB A Stanton
Mar 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·Z Karim-JimenezH Murer
Feb 15, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·L Y NgoJ D Unadkat
May 16, 2003·Current Biology : CB·Marc Symons, Nicole Rusk
Nov 13, 2003·European Journal of Pharmacology·Lara M MangraviteKathleen M Giacomini
Oct 8, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sang-Ho Kwon, William B Guggino
Jun 22, 2006·American Journal of Physiology. Renal Physiology·Mark A EllisOra A Weisz
Apr 6, 2007·American Journal of Physiology. Renal Physiology·Vijaya L DamarajuCarol E Cass
Apr 7, 2007·The Journal of Physiology·Ekaitz Errasti-MurugarrenF Javier Casado
Jul 8, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Roger Y TsangRaymond Lai
Aug 1, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M Pastor-AngladaF J Casado
Oct 2, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ekaitz Errasti-MurugarrenMarçal Pastor-Anglada
Jun 3, 2009·Current Vascular Pharmacology·Míriam Molina-ArcasMarçal Pastor-Anglada

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Citations

Dec 6, 2011·The Biochemical Journal·Itziar Pinilla-MacuaMarçal Pastor-Anglada
Apr 12, 2012·Molecular Pharmacology·Ekaitz Errasti-MurugarrenMarçal Pastor-Anglada
Oct 21, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Paula Fernández-CalottiMarçal Pastor-Anglada
Aug 11, 2020·PLoS Biology·Yanxia ZhouDong Deng
Nov 25, 2020·Chemical Reviews·Nicholas J Wright, Seok-Yong Lee
Nov 10, 2021·Physical Chemistry Chemical Physics : PCCP·Huaichuan DuanJianping Hu

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