The human rhesus-associated rhag protein and a kidney homologue promote ammonium transport in yeast

The human rhesus-associated rhag protein and a kidney homologue promote ammonium transport in yeast

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ABSTRACT The Rhesus blood-group antigens are defined by a complex association of membrane polypeptides that includes the non-glycosylated Rh proteins (RhD and RhCE) and the RHag


glycoprotein, which is strictly required for cell surface expression of these antigens1. RhAG and the Rh polypeptides are erythroid-specific transmembrane proteins belonging to the same


family (36% identity)2,3. Despite their importance in transfusion medicine, the function of RhAG and Rh proteins remains unknown, except that their absence in Rhnull individuals leads to


morphological and functional abnormalities of erythrocytes, known as the Rh-deficiency syndrome. We recently found significant sequence similarity between the Rh family proteins, especially


RhAG, and Mep/Amt ammonium transporters4,5. We show here that RhAG and also RhGK, a new human homologue expressed in kidney cells only, function as ammonium transport proteins when expressed


in yeast. Both specifically complement the growth defect of a yeast mutant deficient in ammonium uptake. Moreover, ammonium efflux assays and growth tests in the presence of toxic


concentrations of the analogue methylammonium indicate that RhAG and RhGK also promote ammonium export. Our results provide the first experimental evidence for a direct role of RhAG and RhGK


in ammonium transport. These findings are of high interest, because no specific ammonium transport system has been characterized so far in human. Access through your institution Buy or


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ACKNOWLEDGEMENTS We thank C. Hattab for help in preparing rabbit antibodies; R. Gaber for yeast strains; and C. Jauniaux and S. Lecomte for technical contributions. This research was


supported by The Commission of the European Communities and the Communauté Française de Belgique, Direction de la Recherche Scientifique. A.-M.M. is Chargé de recherches du Fonds National


belge de la Recherche Scientifique. G.M. is currently a fellow of the International Centre for Genetic Engineering and Biotechnology. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *


Laboratoire de Physiologie Cellulaire, Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires, Gosselies, Belgium Anne-Marie Marini & Bruno André * Unité INSERM


U76, Institut National de la Transfusion Sanguine Paris, France Giorgio Matassi, Virginie Raynal, Jean-Pierre Cartron & Baya Chérif-Zahar * Laboratorio di Evoluzione Molecolare, Stazione


Zoologica “Anton Dohrn”, Naples, Italy Giorgio Matassi Authors * Anne-Marie Marini View author publications You can also search for this author inPubMed Google Scholar * Giorgio Matassi


View author publications You can also search for this author inPubMed Google Scholar * Virginie Raynal View author publications You can also search for this author inPubMed Google Scholar *


Bruno André View author publications You can also search for this author inPubMed Google Scholar * Jean-Pierre Cartron View author publications You can also search for this author inPubMed 


Google Scholar * Baya Chérif-Zahar View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Bruno André or Baya


Chérif-Zahar. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Marini, AM., Matassi, G., Raynal, V. _et al._ The human Rhesus-associated RhAG protein and


a kidney homologue promote ammonium transport in yeast. _Nat Genet_ 26, 341–344 (2000). https://doi.org/10.1038/81656 Download citation * Received: 07 April 2000 * Accepted: 06 September


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