SEARCH:   Advanced

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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 5, 2007 Accepted December 8, 2007 Band 3 Courcouronnes (Ser667Phe): a trafficking mutant differentially rescued by wild type band 3 and glycophorin A Ashley M Toye, Rosalind C Williamson, Moudji Khanfar, Brigitte Bader-Meunier, Therese Cynober, Madeleine Thibault, Gil Tchernia, Michele Dechaux, Jean Delaunay, and Lesley J Bruce* Department of Biochemistry, University of Bristol, Bristol, United Kingdom Maternite Evry, Hopital Louise-Michel, Evry, France Department of Physiology, Hopital Necker-Enfants-Malades, Paris, France Centre de Reference des Maladies Constitutionnelles de l'Erythropoiese et du Globule Rouge, Hopital de Bicetre, Le Kremlin-Bicetre, France INSERM U 779, Hopital de Bicetre, Le Kremlin-Bicetre, France Bristol Institute for Transfusion Sciences, National Blood Service, Bristol, United Kingdom * Corresponding author; email: lesley.bruce{at}nbs.nhs.uk. 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 ~35% of wild-type, other proteins of the band 3/Rh macrocomplex were also reduced. DNA sequence analysis revealed a novel homozygous mutation, C2000 to T, leading to the amino acid substitution, Ser667Phe. The parents were heterozygous for the same mutation. Sulfate influx in the patient's erythrocytes was ~40% wild-type. The mutant band 3 produced very little chloride influx when expressed in Xenopus oocytes. Influx was partially rescued by co-expression of glycophorin A and also rescued by co-expression of wild-type band 3. At age 2 years, an ammonium chloride challenge showed the child has incomplete dRTA. Stable expression of mutant kidney band 3 in both non-polarized and polarized Madin-Darby canine kidney cells showed that the majority 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]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020