Mutations in the band 3 (AE1) gene associated with distal renal tubular acidosis

2001 ◽  
Vol 29 (3) ◽  
pp. A87-A87
Author(s):  
A. M. Toye ◽  
L. J. Bruce ◽  
O. Wrong ◽  
M. T. Young ◽  
R. J. Unwin ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Renal Tubular

Band 3 nullVIENNA, a novel homozygousSLC4A1p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

2016 ◽  
Vol 64 (3) ◽  
pp. e26227 ◽  
Author(s):  
Leo Kager ◽  
Lesley J. Bruce ◽  
Petra Zeitlhofer ◽  
Joanna F. Flatt ◽  
Tabita M. Maia ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Renal Tubular Acidosis ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Renal Tubular

scholarly journals Autosomal Dominant Distal Renal Tubular Acidosis Is Associated in Three Families with Heterozygosity for the R589H Mutation in the AE1 (Band 3) Cl−/HCO3−Exchanger

1998 ◽  
Vol 273 (11) ◽  
pp. 6380-6388 ◽  
Author(s):  
Petr Jarolim ◽  
Chairat Shayakul ◽  
Daniel Prabakaran ◽  
Lianwei Jiang ◽  
Alan Stuart-Tilley ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Autosomal Dominant ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Renal Tubular

scholarly journals Absence of vacuolar H(+)-ATPase pump in the collecting duct of a patient with hypokalemic distal renal tubular acidosis and Sjögren's syndrome.

1995 ◽  
Vol 6 (2) ◽  
pp. 295-301
Author(s):  
P E DeFranco ◽  
L Haragsim ◽  
P G Schmitz ◽  
B Bastani
Keyword(s):  
Renal Biopsy ◽  
Renal Tubular Acidosis ◽  
Collecting Duct ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Hydrogen Ion ◽  
Intercalated Cells ◽  
Band 3 Protein ◽  
Ion Secretion ◽  
Renal Tubular

Distal renal tubular acidosis (dRTA) is a common complication of autoimmune connective tissue diseases. The underlying pathophysiology of renal tubular acidosis in these syndromes is frequently characterized by impaired hydrogen ion secretion, i.e., secretory defect dRTA. However, the precise molecular events leading to this disturbance remain poorly understood. An opportunity was recently afforded to examine the ultrastructural features of the collecting duct in a patient with Sjögren's syndrome and secretory defect dRTA. Immunocytochemical analysis of a renal biopsy obtained 12 months after the patient's initial presentation demonstrated a complete absence of vacuolar H(+)-ATPase in the collecting duct. Antibodies to the 31- and 56-kd kidney-specific subunits of the H(+)-ATPase pump were used to characterize pump distribution. Interestingly, although antiserum to the CI-:HCO3- anion exchanger (band-3 protein) reacted strongly with normal human kidney and the patient's red blood cells, no immunoreactivity was observed in the patient's collecting duct epithelium. Importantly, electron microscopy of the patient's renal biopsy specimen disclosed cells that ultrastructurally were indistinguishable from intercalated cells. These results suggest that the functional basis of impaired hydrogen ion secretion in this patient was secondary to the absence of intact H(+)-ATPase pumps rather than defective pump function or distribution. The presence of intercalated cells ultrastructurally, but the absence of discernible staining for band-3 protein and H(+)-ATPase, also suggests that the defect in proton secretion may represent a defect involving the assembly of at least two of the ion transport pumps essential for the normal maintenance of acid-base homeostasis by the intercalated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Defective kidney anion-exchanger 1 (AE1, Band 3) trafficking in dominant distal renal tubular acidosis (dRTA).

2005 ◽  
Vol 72 ◽  
pp. 47-63 ◽  
Author(s):  
Ashley M. Toye
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Apical Membrane ◽  
Basolateral Membrane ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Anion Exchanger 1 ◽  
C Terminus ◽  
N Terminus ◽  
Renal Tubular

dRTA (distal renal tubular acidosis) results from the failure of the a-intercalated cells in the distal tubule of the nephron to acidify the urine. A truncated form of AE1 (anion-exchanger 1; Band 3), kAE1 (kidney isoform of AE1), is located in the basolateral membrane of the intercalated cell. Mutations in the AE1 gene cause autosomal dominant and recessive forms of dRTA. All the dominant dRTA mutations investigated cause aberrant trafficking of kAE1, resulting in its intracellular retention or mistargeting to the apical plasma membrane. Therefore the intracellular retention of hetero-oligomers containing wild-type and dRTA mutants, or the mistargeted protein in the apical membrane neutralizing acid secretion, explains dominant dRTA. The kAE1 (Arg901→stop) mutant has been studied in more detail, since the mistargeting kAE1 (Arg901→stop) from the basolateral to the apical membrane is consistent with the removal of a basolateral localization signal. The C-terminal amino acids deleted by the Arg901→stop mutation, contain a tyrosine motif and a type II PDZ interaction domain. The tyrosine residue (Tyr904), but not the PDZ domain, is critical for basolateral localization. In the absence of the N-terminus of kAE1, the C-terminus was not sufficient to localize kAE1 to the basolateral membrane. This suggests that a determinant within the kAE1 N-terminus co-operates with the C-terminus for kAE1 basolateral localization. Interestingly, Tyr359, in the N-terminal domain, and Tyr904 in the C-terminus of AE1 are phosphorylated in red blood cells. A potential scheme is suggested where successive phosphorylation of these residues is necessary for correct localization and recycling of kAE1 to the basolateral membrane.

Band 3 Edmonton I, a novel mutant of the anion exchanger 1 causing spherocytosis and distal renal tubular acidosis

2010 ◽  
Vol 426 (3) ◽  
pp. 379-388 ◽  
Author(s):  
Carmen Chu ◽  
Naomi Woods ◽  
Nunghathai Sawasdee ◽  
Helene Guizouarn ◽  
Bernard Pellissier ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Failure To Thrive ◽  
Renal Stones ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Kidney Cells ◽  
Gene Encoding ◽  
Anion Exchanger 1 ◽  
Renal Tubular

dRTA (distal renal tubular acidosis) and HS (hereditary spherocytosis) are two diseases that can be caused by mutations in the gene encoding the AE1 (anion exchanger 1; Band 3). dRTA is characterized by defective urinary acidification, leading to metabolic acidosis, renal stones and failure to thrive. HS results in anaemia, which may require regular blood transfusions and splenectomy. Mutations in the gene encoding AE1 rarely cause both HS and dRTA. In the present paper, we describe a novel AE1 mutation, Band 3 Edmonton I, which causes dominant HS and recessive dRTA. The patient is a compound heterozygote with the new mutation C479W and the previously described mutation G701D. Red blood cells from the patient presented a reduced amount of AE1. Expression in a kidney cell line showed that kAE1 (kidney AE1) C479W is retained intracellularly. As kAE1 is a dimer, we performed co-expression studies and found that, in kidney cells, kAE1 C479W and G701D proteins traffic independently from each other despite their ability to form heterodimers. Therefore the patient carries one kAE1 mutant that is retained in the Golgi (G701D) and another kAE1 mutant (C479W) located in the endoplasmic reticulum of kidney cells, and is thus probably unable to reabsorb bicarbonate into the blood. We conclude that the C479W mutant is a novel trafficking mutant of AE1, which causes HS due to a decreased cell-surface AE1 protein and results in dRTA due to its intracellular retention in kidney.

scholarly journals Red Blood Cell AE1/Band 3 Transports in Dominant Distal Renal Tubular Acidosis Patients

2020 ◽  
Vol 5 (3) ◽  
pp. 348-357 ◽  
Author(s):  
Jean-Philippe Bertocchio ◽  
Sandrine Genetet ◽  
Lydie Da Costa ◽  
Stephen B. Walsh ◽  
Bertrand Knebelmann ◽  
...  
Keyword(s):  
Blood Cell ◽  
Renal Tubular Acidosis ◽  
Red Blood Cell ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Renal Tubular

scholarly journals Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene.

1997 ◽  
Vol 100 (7) ◽  
pp. 1693-1707 ◽  
Author(s):  
L J Bruce ◽  
D L Cope ◽  
G K Jones ◽  
A E Schofield ◽  
M Burley ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Red Cell ◽  
Renal Tubular

scholarly journals Band 3 Walton, a C-terminal deletion associated with distal renal tubular acidosis, is expressed in the red cell membrane but retained internally in kidney cells

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 342-347 ◽  
Author(s):  
Ashley M. Toye ◽  
Lesley J. Bruce ◽  
Robert J. Unwin ◽  
Oliver Wrong ◽  
Michael J. A. Tanner
Keyword(s):  
Cell Surface ◽  
Renal Tubular Acidosis ◽  
Band 3 ◽  
Normal Band ◽  
Distal Renal Tubular Acidosis ◽  
Mutant Protein ◽  
Kidney Cells ◽  
Kidney Cell Line ◽  
Transport Activity ◽  
Renal Tubular

Human band 3 Walton is an AE1 mutation that results in the deletion of the 11 COOH-terminal amino acids of the protein and is associated with dominant distal renal tubular acidosis. The properties of band 3 Walton expressed with normal band 3 in the heterozygous mutant erythrocytes and the kidney isoform expressed in Xenopusoocytes and in the Madin-Darby canine kidney cell line were examined. The mutant erythrocytes have normal hematology but have reduced band 3 Walton content. Transport studies showed that erythrocyte band 3 Walton has normal sulfate transport activity, and kidney band 3 Walton has normal chloride transport activity when expressed inXenopus oocytes. The mutant protein is clearly able to reach the cell surface of erythrocytes and oocytes. In contrast, while normal kidney band 3 was expressed at the cell surface in the kidney cell line, the Walton mutant protein was retained intracellularly within the kidney cells. The results demonstrate that band 3 Walton is targeted differently in erythrocytes and kidney cells and indicate that the COOH-terminal tail of band 3 is required to allow movement to the cell surface in kidney cells. It is proposed here that the mutant band 3 gives rise to dominant distal renal tubular acidosis by inhibiting the movement of normal band 3 to the cell surface. It is suggested that this results from the association of the normal and mutant proteins in band 3 hetero-oligomers, which causes the intracellular retention of normal band 3 with the mutant protein.

scholarly journals Incomplete distal renal tubular acidosis coinherited with a mutation in the band 3 (AE1) gene

1997 ◽  
Vol 12 (9) ◽  
pp. 1869-1873 ◽  
Author(s):  
R. Rysava ◽  
V. Tesar ◽  
M. Jirsa ◽  
V. Brabec ◽  
P. Jarolim
Keyword(s):  
Renal Tubular Acidosis ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Renal Tubular

The association between familial distal renal tubular acidosis and mutations in the red cell anion exchanger (band 3, AE1) gene

1998 ◽  
Vol 76 (5) ◽  
pp. 723-728 ◽  
Author(s):  
Lesley J Bruce ◽  
Robert J Unwin ◽  
Oliver Wrong ◽  
Michael JA Tanner
Keyword(s):  
Renal Tubular Acidosis ◽  
Anion Exchanger ◽  
Autosomal Dominant ◽  
Collecting Duct ◽  
Band 3 ◽  
Distal Renal Tubular Acidosis ◽  
Xenopus Laevis Oocytes ◽  
Red Cell ◽  
Transport Activity ◽  
Renal Tubular

In distal renal tubular acidosis (dRTA) the tubular secretion of hydrogen ion in the distal nephron is impaired, leading to the development of metabolic acidosis, frequently accompanied by hypokalemia, nephrocalcinosis, and metabolic bone disease. The condition can be familial, when it is usually inherited as an autosomal dominant, though there is a rarer autosomal recessive form associated with nerve deafness. It has been shown that the autosomal dominant form of dRTA is associated with a defect in the anion exchanger (AE1) of the renal collecting duct intercalated cell. This transporter is a product of the same gene (AE1) as the erythrocyte anion exchanger, band 3. In this review we will look at the evidence for this association. Studies of genomic DNA from families with this disorder have shown, both by genetic linkage studies and by DNA sequencing, that affected individuals are heterozygous for mutations in the AE1 gene whilst unaffected family members have a normal band 3 sequence. Mutations have been found in the region of proposed helices 6 and 7 of the membrane domain of band 3 and involve amino acids Arg-589 and Ser-613, and in the COOH-terminal domain of band 3. Studies of red cell band 3 from these families have provided information on the effect these mutations have on the structure and function of erythrocyte band 3. Expression studies of the erythroid and kidney isoforms of the mutant AE1 proteins, in Xenopus laevis oocytes, have shown that they retained chloride transport activity, suggesting that the disease in the dRTA families is not related simply to the anion transport activity of the mutated proteins. A possible explanation for the dominant effect of these mutant AE1 proteins in the kidney cell is that these mutations affect the targeting of AE1 from the basolateral to the apical membrane of the alpha-intercalated cell.Key words: erythrocyte, kidney, acidosis.

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