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Blood, 1 June 2008, Vol. 111, No. 11, pp. 5380-5389. Prepublished online as a Blood First Edition Paper on January 3, 2008; DOI 10.1182/blood-2007-07-099473. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-07-099473v1 111/11/5380    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 Toye, A. M. Articles by Bruce, L. J. Search for Related Content PubMed PubMed Citation Articles by Toye, A. M. Articles by Bruce, L. J. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Band 3 Courcouronnes (Ser667Phe): a trafficking mutant differentially rescued by wild-type band 3 and glycophorin A Ashley M. Toye1, Rosalind C. Williamson1, Moudji Khanfar2, Brigitte Bader-Meunier3, Thérèse Cynober4, Madeleine Thibault4, Gil Tchernia4, Michèle Déchaux3, Jean Delaunay4,5, and Lesley J. Bruce6 1 Department of Biochemistry, University of Bristol, Bristol, United Kingdom; 2 Hôpital Louise-Michel, Evry, France; 3 Hôpital Necker-Enfants-Malades, Paris, France; 4 Centre de Référence des Maladies Constitutionnelles de l'Erythropoïèse et du Globule Rouge, Hôpital de Bicêtre, Assistance Publique des Hopitaux de Paris (APHP), Le Kremlin Bicetre, France; 5 Inserm U 779, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France; and 6 Bristol Institute for Transfusion Sciences, National Blood Service, Bristol, United Kingdom We describe a mutation in human erythrocyte band 3 (anion exchanger 1; SLC4A1) causing both hereditary spherocytosis and distal renal tubular acidosis. The proband developed a transfusion-dependent, hemolytic anemia following birth. Immunoblotting showed band 3 was reduced to approximately 35% of wildtype; other proteins of the band 3/Rh macrocomplex were also reduced. DNA sequence analysis revealed a novel homozygous mutation, c.2000C>T, leading to the amino acid substitution Ser667Phe. The parents were heterozygous for the same mutation. Sulfate influx in the patient's erythrocytes was approximately 40% wild type. The mutant band 3 produced very little chloride influx when expressed in Xenopus oocytes. Influx was partially rescued by coexpression of glycophorin A and also rescued by coexpression of wild-type band 3. At 2 years of age, an ammonium chloride challenge showed the child has incomplete distal renal tubular acidosis (dRTA). Stable expression of mutant kidney band 3 in both nonpolarized and polarized Madin-Darby canine kidney cells showed that most of the mutant protein was retained in the endoplasmic reticulum. Overall our results suggest that the Ser667Phe does not affect the anion transport function of band 3, but causes a trafficking defect in both erythrocytes and kidney cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. L. Alper Molecular physiology and genetics of Na+-independent SLC4 anion exchangers J. Exp. Biol., June 1, 2009; 212(11): 1672 - 1683. [Abstract] [Full Text] [PDF] R. Rollason, V. Korolchuk, C. Hamilton, M. Jepson, and G. Banting A CD317/tetherin-RICH2 complex plays a critical role in the organization of the subapical actin cytoskeleton in polarized epithelial cells J. Cell Biol., March 9, 2009; 184(5): 721 - 736. [Abstract] [Full Text] [PDF] R. C. Williamson, A. C. N. Brown, W. J. Mawby, and A. M. Toye Human kidney anion exchanger 1 localisation in MDCK cells is controlled by the phosphorylation status of two critical tyrosines J. Cell Sci., October 15, 2008; 121(20): 3422 - 3432. [Abstract] [Full Text] [PDF]

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