SEARCH:   Advanced

Blood, 5 February 2009, Vol. 113, No. 6, pp. 1350-1357. Prepublished online as a Blood First Edition Paper on October 17, 2008; DOI 10.1182/blood-2008-07-171140. This Article Full Text Full Text (PDF) Supplemental Methods and Figures Supplemental Methods and Figures All Versions of this Article: blood-2008-07-171140v1 113/6/1350    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bruce, L. J. Articles by Stewart, G. W. Search for Related Content PubMed PubMed Citation Articles by Bruce, L. J. Articles by Stewart, G. W. Related Collections Transfusion Medicine Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS The monovalent cation leak in overhydrated stomatocytic red blood cells results from amino acid substitutions in the Rh-associated glycoprotein Lesley J. Bruce1, Hélène Guizouarn2, Nicholas M. Burton1,3, Nicole Gabillat2, Joyce Poole1, Joanna F. Flatt1, R. Leo Brady3, Franck Borgese2, Jean Delaunay4, and Gordon W. Stewart5 1 Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant, Bristol, United Kingdom; 2 Laboratoire de Biologie et Physiopathologie des Systèmes Intégrés, FRE3094 CNRS-Université de Nice, Nice, France; 3 Department of Biochemistry, University of Bristol, Bristol, United Kingdom; 4 Hématologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris; Faculté de Médecine Paris-Sud, Universite Paris-Sud, Inserm U779, Le Kremlin-Bicêtre, France; and 5 Department of Medicine, University College London, London, United Kingdom Overhydrated hereditary stomatocytosis (OHSt) is a rare dominantly inherited hemolytic anemia characterized by a profuse membrane leak to monovalent cations. Here, we show that OHSt red cell membranes contain slightly reduced amounts of Rh-associated glycoprotein (RhAG), a putative gas channel protein. DNA analysis revealed that the OHSt patients have 1 of 2 heterozygous mutations (t182g, t194c) in RHAG that lead to substitutions of 2 highly conserved amino acids (Ile61Arg, Phe65Ser). Unexpectedly, expression of wild-type RhAG in Xenopus laevis oocytes induced a monovalent cation leak; expression of the mutant RhAG proteins induced a leak about 6 times greater than that in wild type. RhAG belongs to the ammonium transporter family of proteins that form pore-like structures. We have modeled RhAG on the homologous Nitrosomonas europaea Rh50 protein and shown that these mutations are likely to lead to an opening of the pore. Although the function of RhAG remains controversial, this first report of functional RhAG mutations supports a role for RhAG as a cation pore. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Mairhofer, M. Steiner, U. Salzer, and R. Prohaska Stomatin-like Protein-1 Interacts with Stomatin and Is Targeted to Late Endosomes J. Biol. Chem., October 16, 2009; 284(42): 29218 - 29229. [Abstract] [Full Text] [PDF] J. F. Flatt and L. J. Bruce The hereditary stomatocytoses Haematologica, August 1, 2009; 94(8): 1039 - 1041. [Full Text] [PDF] G. C. Kodippili, J. Spector, C. Sullivan, F. A. Kuypers, R. Labotka, P. G. Gallagher, K. Ritchie, and P. S. Low Imaging of the diffusion of single band 3 molecules on normal and mutant erythrocytes Blood, June 11, 2009; 113(24): 6237 - 6245. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020