Band 3 Courcouronnes (Ser667Phe): a trafficking mutant differentially rescued by wild-type band 3 and glycophorin A
Open Access
- 1 June 2008
- journal article
- case report
- Published by American Society of Hematology in Blood
- Vol. 111 (11) , 5380-5389
- https://doi.org/10.1182/blood-2007-07-099473
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- Misfolded Proteins Traffic from the Endoplasmic Reticulum (ER) Due to ER Export SignalsMolecular Biology of the Cell, 2007
- Immunohistochemical comparison of a case of inherited distal renal tubular acidosis (with a unique AE1 mutation) with an acquired case secondary to autoimmune diseaseNephrology Dialysis Transplantation, 2007
- INCIDENCE OF HEREDITARY SPHEROCYTOSIS IN A POPULATION OF JAUNDICED NEONATESPediatric Hematology and Oncology, 2006
- A band 3-based macrocomplex of integral and peripheral proteins in the RBC membraneBlood, 2003
- Novel AE1 mutations in recessive distal renal tubular acidosis. Loss-of-function is rescued by glycophorin A.Journal of Clinical Investigation, 1998
- Hematologically Important Mutations: Band 3 and Protein 4.2 Variants in Hereditary SpherocytosisBlood Cells, Molecules, and Diseases, 1997
- Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene.Journal of Clinical Investigation, 1997
- Targeted disruption of the murine erythroid band 3 gene results in spherocytosis and severe haemolytic anaemia despite a normal membrane skeletonNature Genetics, 1996
- Anion Exchanger 1 (Band 3) Is Required to Prevent Erythrocyte Membrane Surface Loss but Not to Form the Membrane SkeletonCell, 1996
- Co-expressed Complementary Fragments of the Human Red Cell Anion Exchanger (Band 3, AE1) Generate Stilbene Disulfonate-sensitive Anion TransportJournal of Biological Chemistry, 1995