Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloride/base exchange activity has been detected in every mammalian nephron segment in which it has been sought. However, in contrast to the Cl-/HCO3- exchanger AE1 in type A intercalated cells, localization of AE2 within the kidney has not been reported. We therefore studied AE2 expression in rat kidney. AE2 mRNA was present in cortex, outer medulla, and inner medulla. Semiquantitative polymerase chain reaction of cDNA from microdissected tubules revealed AE2 cDNA levels as follows [copies of cDNA derived per mm tubule (+/- SE)]: proximal convoluted tubule, 688 +/- 161; proximal straight tubule, 652 +/- 189; medullary thick ascending limb, 1,378 +/- 226; cortical thick ascending limb, 741 +/- 24; cortical collecting duct, 909 +/- 71; and outer medullary collecting duct, 579 +/- 132. AE2 cDNA was also amplified in thin limbs and in inner medullary collecting duct. AE2 polypeptide was detected in all kidney regions. AE2 mRNA and protein were also detected in several renal cell lines. The data are compatible with the postulated roles of AE2 in maintenance of intracellular pH and chloride concentration and with its possible participation in transepithelial transport.
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PMID:Regional and segmental localization of AE2 anion exchanger mRNA and protein in rat kidney. 748 30

Acid-secreting intercalated cells of the kidney collecting duct and tumor cells of renal oncocytoma express an anion exchanger that is immunologically related but not identical to the chloride-bicarbonate anion exchanger of erythrocytes (AE1). In this study, we have mapped the binding site of a monoclonal antibody against erythroid AE1 that does not react with either intercalated cells or oncocytoma. The epitope is located close to the NH2 terminus of AE1, indicating that AE1 in intercalated cells and oncocytoma differs in its NH2 terminus from erythroid AE1. This conclusion was supported by an antibody directed against residues 1-14 of erythroid AE1 that does not react with intercalated cells in oncocytoma. Polymerase chain reaction performed with mRNA from a human kidney revealed that the sequence containing the codons for Met-1 and Met-33 in erythroid mRNA is missing in the kidney transcript, whereas the sequence coding for Met-66 is present. DNA sequence data derived from cloning the 5' end of the human kidney AE1 mRNA clearly showed that the 5' untranslated region comprises part of intron 3, the complete exon 4 that is followed by exon 5 containing Met-66 as the site of translation initiation. Altogether, the results indicate that AE1 in the human kidney is an amino-terminally truncated form of erythroid AE1 that is restricted to the basolateral membrane domain of the acid-secreting intercalated cells of the collecting duct and is also expressed in oncocytoma.
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PMID:Anion exchanger 1 in human kidney and oncocytoma differs from erythroid AE1 in its NH2 terminus. 750 71

Many renal diseases involving the tubular epithelium appear to preferentially affect certain nephron segments. While major portions of the nephron, such as proximal and distal convoluted tubules and collecting ducts, can be identified in the normal kidney, the distinction of diseased nephron segments can be difficult in tissue sections. Thus, to identify which nephron segments are involved in pathologic changes is usually impossible by routine histologic examination alone. Recently antibody and lectin probes that react with specific nephron segment-specific epitopes and carbohydrates, respectively, have become available. Some of these antibodies and lectins can be used on formalin-fixed, paraffin-embedded, archival tissues. Because renal tubules appear to retain their nephron segment-specific epitopes and glycoprotein moieties under most pathologic conditions, these nephron segment-specific tubular epithelial markers provide a method to study renal diseases involving the tubular system also in archival material. Such nephron segment-specific tubular epithelial markers are: the lectins, Tetragonolobus purpuras and Phaseolus vulgaris erythroagglutinin (proximal tubular markers); antibodies to low-molecular-weight cytokeratin (AE1/AE3); epithelial membrane antigen and the lectin Arachis hypogaea (distal nephron [distal convoluted tubule and collecting duct] markers); and antibodies to Tamm-Horsfall protein (labeling the thick ascending limb of Henle). We review the application of these and other renal tubular epithelial markers in the normal kidney and in various renal diseases including cystic disease of the kidney, interstitial nephritis, tubular atrophy, acute tubular necrosis, myeloma cast nephropathy, and renal tumors.
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PMID:Immunohistochemical and lectin dissection of the human nephron in health and disease. 825 Jun 94

There are two types of intercalated cells of the renal collecting duct; one secretes H+ and the other secretes HCO3-. The H(+)-secreting form has an apical vacuolar H(+)-ATPase and a basolateral Cl/HCO3 exchanger that cross-reacts with antibodies to band 3, the product of the AE1 gene. The HCO3(-)-secreting form has a basolateral vacuolar H(+)-ATPase and an apical Cl/HCO3 exchanger, whose identity has not been established previously. Apical membrane vesicles of beta intercalated cells purified from rabbit kidney cortex contain both an electroneutral Cl/HCO3 exchange activity and polypeptides that react with antibodies to band 3 on Western blots. Furthermore, both primary cultures of HCO3(-)-secreting intercalated cells and an immortalized cell line derived from these cells express AE1 and have an apical Cl/HCO3 exchanger. Apical membranes purified from these cells contain a 100-kDa polypeptide that cross-reacts with antibody to the cytoplasmic domain of band 3. These data suggest that the apical Cl/HCO3 exchanger of HCO3(-)-secreting intercalated cells is band 3.
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PMID:The apical Cl/HCO3 exchanger of beta intercalated cells. 849 83

The kidneys of mice (CAR2-null mice) that are genetically devoid of carbonic anhydrase type II (CAII) were screened by immunocytochemistry with antibodies that distinguish intercalated and principal cells. Immunofluorescent localization of the anion exchanger AE1 and of the 56-kDa subunit of the vacuolar H(+)-adenosinetriphosphatase (H(+)-ATPase) was used to identify intercalated cells, while the AQP2 water channel was used as a specific marker for principal cells of the collecting duct. The CAII deficiency of the CAR2-null mice was first confirmed by the absence of immunofluorescent staining of kidney sections exposed to an anti-CAII antibody. Cells positive for AE1 and H(+)-ATPase were common in all collecting duct regions in normal mice but were virtually absent from the inner stripe of the outer medulla and the inner medulla of CAR2-null mice. The number of positive cells was also reduced threefold in the cortical collecting duct of CAR2-null animals compared with normal mice. In parallel, the percentage of AQP2-positive cells was correspondingly increased in the collecting tubules of CAII-deficient mice, whereas the total number of cells per tubule remained unchanged. These results suggest that intercalated cells are severely depleted and are replaced by principal cells in CAII-deficient mice. Quantitative analysis and double staining showed that, in the cortex, both type A and type B intercalated cells are equally affected. Elucidation of the mechanism(s) responsible for this phenotype will be of importance in understanding the origin and development of intercalated cells in the kidney.
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PMID:Depletion of intercalated cells from collecting ducts of carbonic anhydrase II-deficient (CAR2 null) mice. 859 70

The AE1 gene is expressed in erythrocytes and the A-type intercalated cells of the kidney distal collecting duct. Although the 5' end of the principal transcript expressed in murine erythroid cells has previously been mapped to a cluster of transcription start sites located immediately upstream of exon 1, the 5' end of the mouse kidney transcript has not been identified. Using the anchored polymerase chain reaction technique to analyze mouse kidney AE1 mRNA, we identified an internal transcription start site located within erythroid intron 3. This site defines an exon of 37 nucleotides that forms the 5' end of the mouse kidney AE1 transcript. AE1 transcripts beginning at this internal start site could not be detected in RNA isolated from purified erythroid progenitor cells or from erythroid cells undergoing erythropoietin-dependent terminal maturation, although transcripts derived from the upstream site were abundant, indicating that only the upstream promoter is active during erythropoiesis. Transient expression of reporter constructs in erythroid and nonerythroid cell lines identified a proximal upstream region of approximately 135 nucleotides that was active as a basal promoter. However, an additional approximately 200 nucleotides of upstream sequence was required for induced levels of activity in erythroid cells. Although our functional approach does not yet indicate the precise sequences required for erythroid induction, the AE1 gene upstream region contains potential GATA sites at -154, -141, and -60; an E-box at -163; CACCC or GGTGG motifs at -188, -121, and -88; and an AP-1/NF-E2-like site at -42.
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PMID:Identification of the proximal erythroid promoter region of the mouse anion exchanger gene. 897 42

The cortical collecting duct (CCD) mediates net secretion or reabsorption of protons according to systemic acid/base status. Using indirect immunofluorescence, we examined the localization and abundance of the vacuolar H(+)-ATPase and the AE1 anion exchanger in intercalated cells (IC) of rat kidney connecting segment (CNT) and CCD during acute (6 hr) metabolic (NH4Cl) acidosis and respiratory (NaHCO3) alkalosis. AE1 immunostaining intensity quantified by confocal microscopy was elevated in metabolic acidosis and substantially reduced in metabolic alkalosis. AE1 immunostaining was restricted to Type A IC in all conditions, and the fraction of AE1+IC was unchanged in CNT and CCd. Metabolic acidosis was accompanied by redistribution of H(+)-ATPase immunostaining towards the apical surface of IC, and metabolic alkalosis was accompanied by H(+)-ATPase redistribution towards the basal surface of IC. Therefore, acute metabolic acidosis produced changes consistent with increased activity of Type A IC and decreased activity of Type B IC, whereas acute metabolic alkalosis produced changes corresponding to increased activity of Type B IC and decreased activity of Type A IC. These data demonstrate that acute systemic acidosis and alkalosis modulate the cellular distribution of two key transporters involved in proton secretion in the distal nephron.
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PMID:Regulation of AE1 anion exchanger and H(+)-ATPase in rat cortex by acute metabolic acidosis and alkalosis. 899 26

We have studied the molecular defect underlying band 3 deficiency in one family with hereditary spherocytosis using nonradioactive single strand conformation polymorphism of polymerase chain reaction (PCR) amplified genomic DNA of the AE1 gene. By direct sequencing, a single base substitution in the splicing donor site of intron 8 (position + 1G --> T) was identified. The study of the cDNA showed a skipping of exon 8. This exon skipping event is responsible for a frameshift leading to a premature stop codon 13 amino acids downstream. The distal urinary acidification test by furosemide was performed to verify the consequences of the band 3 deficiency in alpha intercalated cortical collecting duct cells (alphaICCDC). We found an increased basal urinary bicarbonate excretion, associated with an increased basal urinary pH and an efficient distal urinary acidification. We also tested the consequences of band 3 deficiency on the Na+/H+ exchanger, by the measurement of Na+/Li+ countertransport activity in red blood cells. The Na+/Li+ countertransport activity was increased threefold to sixfold in the patients compared with the controls. It is possible that band 3 deficiency in the kidney leads to a decrease in the reabsorption of HCO3- in alphaICCDC and anion loss, which might be associated with an increased sodium-lithium countertransport activity.
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PMID:Band 3 Campinas: a novel splicing mutation in the band 3 gene (AE1) associated with hereditary spherocytosis, hyperactivity of Na+/Li+ countertransport and an abnormal renal bicarbonate handling. 932 49

Distal renal tubular acidosis (dRTA) is characterized by defective urinary acidification by the distal nephron. Cl-/HCO3- exchange mediated by the AE1 anion exchanger in the basolateral membrane of type A intercalated cells is thought to be an essential component of lumenal H+ secretion by collecting duct intercalated cells. We evaluated the AE1 gene as a possible candidate gene for familial dRTA. We found in three unrelated families with autosomal dominant dRTA that all clinically affected individuals were heterozygous for a single missense mutation encoding the mutant AE1 polypeptide R589H. Patient red cells showed approximately 20% reduction in sulfate influx of normal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid sensitivity and pH dependence. Recombinant kidney AE1 R589H expressed in Xenopus oocytes showed 20-50% reduction in Cl-/Cl- and Cl-/HCO3- exchange, but did not display a dominant negative phenotype for anion transport when coexpressed with wild-type AE1. One apparently unaffected individual for whom acid-loading data were unavailable also was heterozygous for the mutation. Thus, in contrast to previously described heterozygous loss-of-function mutations in AE1 associated with red cell abnormalities and apparently normal renal acidification, the heterozygous hypomorphic AE1 mutation R589H is associated with dominant dRTA and normal red cells.
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PMID: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. 949 68

The cortical collecting duct (CCD) B cell possesses an apical anion exchanger dissimilar to AE1, AE2, and AE3. The purpose of these studies was to characterize this transporter more fully by examining its regulation by CO2 and HCO3. We measured intracellular pH (pHi) in single intercalated cells of in vitro microperfused CCD using the fluorescent, pH-sensitive dye, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). In the absence of extracellular CO2/HCO3, luminal Cl removal caused reversible intracellular alkalinization, identifying this transporter as a Cl/base exchanger able to transport bases other than HCO3. Adding extracellular CO2/HCO3 decreased B cell pHi while simultaneously increasing Cl/base exchange activity. Since intracellular acidification inhibits AE1, AE2, and AE3, we examined mechanisms other than pHi by which the stimulation occurred. These studies showed that B cell apical anion exchange activity was CO2 stimulated and carbonic anhydrase dependent. Moreover, the stimulation was independent of luminal bicarbonate, luminal pH or pHi, and changes in buffer capacity. We conclude that the B cell possesses an apical Cl/base exchanger whose activity is regulated by CO2-stimulated, carbonic anhydrase-dependent cytoplasmic HCO3 formation.
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PMID:Regulation of B-type intercalated cell apical anion exchange activity by CO2/HCO3-. 984


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