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)

The localization of two glucose transporter isoforms was mapped in the rat kidney: the high-Michaelis constant (Km; 15-20 mM) low-affinity "liver" transporter and the low-Km (1-2 mM) high-affinity "erythroid/brain" transporter. Both are basolateral membrane proteins, but the liver transporter was present exclusively in the S1 part of the proximal tubule, whereas the erythroid/brain transporter was expressed at variable levels in different nephron segments. Staining intensity was low in the straight proximal tubule (S3), intermediate in the medullary thin and thick ascending limbs, and highest in connecting segments and collecting ducts. In the collecting duct, the erythroid/brain glucose transporter was expressed at the highest level in intercalated cells; less was present in principal cells. In the papilla, only intercalated cells expressed this transporter isoform. These results suggest specific involvements of each transporter isoform in transepithelial glucose reabsorption by different segments of the proximal tubule. They also indicate that while the liver glucose transporter is present in gluconeogenic cells, there is a good correlation between the level of expression of the erythroid/brain glucose transporter and the glycolytic activity of the different nephron segments.
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PMID:Differential localization of two glucose transporter isoforms in rat kidney. 226 Jun 38

The cellular distributions of the kidney form of the erythrocyte band 3 chloride/bicarbonate exchanger and the kidney vacuolar H+-transporting ATPase were examined in rat kidney collecting duct by immunocytochemical staining of adjacent semithin sections. Polyclonal anti-peptide antibodies directed against two regions of murine erythroid band 3 gave a pattern of basolateral labeling similar to that seen with antibodies directed against the entire protein. In the medullary collecting duct almost all intercalated cells expressed basolateral membrane band 3 and displayed apical membrane H+-ATPase. In the cortical collecting duct and the connecting segment, band 3 labeling was restricted to a subpopulation of intercalcated cells. In the cortical collecting duct 46% of intercalated cells had apical H+-ATPase and basolateral band 3. Cells that had either basolateral or diffuse cytoplasmic staining for H+-ATPase were all band 3-negative and accounted for 53% of the intercalated cells. In addition, occasional intercalated cells with apical H+-ATPase appeared to lack basolateral band 3. These results demonstrate the coexpression of H+-ATPase and band 3 in opposite plasma membrane domains of a subpopulation of intercalated cells that are probably the acid-excreting (type A) cells. All other intercalated cells lacked immunoreactive band 3 and probably include the bicarbonate-excreting (type B) cells.
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PMID:Subtypes of intercalated cells in rat kidney collecting duct defined by antibodies against erythroid band 3 and renal vacuolar H+-ATPase. 252 38

Poly- and monoclonal antibodies have been prepared against the cytoplasmic domain (43 kDa) and the 17-, 20-, and 35-kDa fragments of the membrane-spanning domain of the human erythrocyte anion exchanger, band 3. The antibodies were used to localize and further characterize analogues of band 3 in the human kidney. We report here that the basolateral membrane of intercalated cells of the connecting tubules and collecting ducts contains an analogue of band 3 that appears to be highly homologous to the erythrocyte anion exchanger. This band 3-like protein is probably important for reabsorption of bicarbonate in the collecting duct system and thus for acidification of the forming urine. The band 3-like protein of the intercalated cells contain immunoreactive sites of both the cytoplasmic domain and the three major fragments of the membrane-spanning domain of erythrocyte band 3. Although no immunological differences were detected between the membrane-spanning domains of band 3 in erythrocytes and intercalated cells, there are at least three sites along the cytoplasmic domain of kidney band 3 that differ from erythrocyte band 3 in either amino acid composition or posttranslational modifications. The main kidney analogue of band 3 that contains epitopes of the cytoplasmic domain as well as the 17- and 35-kDa membrane-spanning domain of erythroid band 3 is a polypeptide with an apparent molecular mass of 100-110 kDa. Further immunoreactive polypeptides at approximately 180, approximately 140, approximately 38, approximately 25-30 kDa that were detected at lower stringency and higher sensitivity of the immunoblotting procedure may be members of a multigene family that encodes a series of related proteins.
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PMID:Immunochemical characterization of a band 3-like anion exchanger in collecting duct of human kidney. 361 86

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

The tissue distribution of mRNA encoding rat kidney water channel CHIP28k was determined by in situ hybridization. cDNA encoding rat kidney CHIP28k was isolated by homology to human erythrocyte CHIP28 (G. M. Preston and P. Agre. Proc. Natl. Acad. Sci. USA 88: 11110-11114, 1991) and used to construct 155-base 35S-labeled cRNA sense and antisense probes corresponding to base pair 7-162. Fixed and frozen tissues were cut in 6- to 12- microns sections, hybridized with probes at 55 degrees C for 16 h, and exposed for 5-9 days. In renal cortex, CHIP28k mRNA was detected intensely on proximal tubule epithelial cells but not in glomeruli or collecting duct. Hybridization to proximal tubule was strongest in deep renal cortex. In no study was there significant hybridization of sense cRNA probe. In renal papilla, CHIP28k mRNA was detected in only a fraction of tubules corresponding to thin limbs of Henle. Hybridization in spleen was observed in red splenic pulp containing erythroid precursors but not in white pulp. In colon, there was selective hybridization in crypt epithelial cells but not in villus epithelial cells or nonepithelial structures. In lung, hybridization was observed in alveolar epithelial cells. In eye, there was selective hybridization in corneal endothelium and ciliary body. No hybridization was observed in any cell types in liver. Northern analysis revealed a 2.8-kilobase mRNA encoding CHIP28k in kidney cortex and papilla but not in brain, skeletal muscle, and liver. These results indicate a wide and highly selective tissue distribution of mRNA encoding the CHIP28k water channel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue-specific expression of mRNA encoding rat kidney water channel CHIP28k by in situ hybridization. 767 51

A rapid passive urea transport has been previously described in the mammalian renal inner medullary collecting duct epithelial cells and in mammalian erythrocytes. Recently, a vasopressin-regulated urea transporter (UT2) has been cloned from a rabbit kidney medullary cDNA library (You, G., Smith, C. P., Kanai, Y., Lee, W. S., Stelzner, M., and Hediger, M. A. (1993) Nature 365, 844-847). We now report the cloning and characterization of a complementary DNA (HUT11) encoding an urea transporter isolated from a human bone marrow library. It encodes a 43,000-Da polypeptide of 391 amino acids that exhibited 63% sequence identity with the rabbit urea transporter and a similar membrane topology. HUT11 carries 2 putative glycosylation sites and 10 cysteines, of which only 7 are conserved at an equivalent position in UT2. HUT11 transcripts have been identified in human erythroid and renal tissues. Expression studies in Xenopus oocytes demonstrated that HUT11 mediates a facilitated urea transport that was inhibited, as described in mammalian erythrocytes, by very low concentrations of phloretin, p-chloromercuribenzene sulfonate, and urea analogues. No unidirectional movements of charged molecules, glycerol, or water were associated with HUT11 expression in oocytes. These findings suggest that HUT11 is most likely responsible for the facilitated urea transport in human red blood cells.
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PMID:Cloning and functional expression of a urea transporter from human bone marrow cells. 798 37

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

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.
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PMID:The association between familial distal renal tubular acidosis and mutations in the red cell anion exchanger (band 3, AE1) gene. 1035 4

Two non-erythroid members of the erythrocyte Rhesus (Rh) protein family, RhBG and RhCG, have been recently cloned in the kidney. These proteins share homologies with specific NH(3)/NH(4)(+) transporters (Mep/Amt) in primitive organisms and plants. When expressed in a Mep-deficient yeast, RhCG can function as a bidirectional NH(3)/NH(4)(+) transporter. The aim of this study was to determine the intrarenal and intracellular location of RhCG in rat kidney. RT-PCR on microdissected rat nephron segments demonstrated expression of mRNAs encoding RhCG in distal convoluted tubules, connecting ducts, and cortical and outer medullary collecting ducts but not in proximal tubules and thick ascending limbs of Henle's loop. Immunolocalization studies performed on rat kidney sections with rabbit anti-human RhCG 31 to 48 antibody showed labeling of the apical pole of tubular cells within the cortex, the outer medulla, and the upper portion of the inner medulla. All cells within connecting tubules had identical apical staining. In cortical collecting ducts, a subpopulation of cells that has either apical staining (alpha-intercalated cells) or diffuse staining (beta-intercalated cells) for the beta1 subunit of the H(+)-ATPase, was heavily stained at their apical pole with the RhCG antibody while principal cells identified as H(+)-ATPase negative cells showed a faint apical staining for RhCG that was much less intense than in adjacent intercalated cells. In the outer medulla and the upper portion of the inner medulla, RhCG labeling was restricted to a subpopulation of cells within the collecting duct that apically express the beta1 subunit of the H(+)-ATPase, indicating that RhCG expression in medullary collecting ducts is restricted to intercalated cells. No labeling was seen in glomeruli, proximal tubules, and limbs of Henle's loop. Immunoblotting of apical membrane fractions from rat kidney cortex with the rabbit anti-human RhCG 31 to 48 antibody revealed a doublet band at approximatively 65 kD.
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PMID:Expression of RhCG, a new putative NH(3)/NH(4)(+) transporter, along the rat nephron. 1213 30

The Rhesus (Rh) glycoproteins, originally described in human blood cells, are mostly recognized for their immunogenic characteristics and importance in pregnancy. The Rh proteins in the red blood cell are expressed as an "Rh complex" made up of one D-subunit, one CE-subunit and two Rh-associated glycoprotein (RhAG) subunits. In addition to its antigenic property, the Rh complex is thought to contribute to membrane stability and structure of red blood cells. The exact function is yet to be determined. Recently, two non-erythroid Rh glycoproteins were cloned from mice (Rhcg and Rhbg) and humans (RhCG and RhBG). RhCG is expressed at the membrane surface alone with no apparent need for heteromeric interaction with other glycoproteins. It is more similar to RhAG than to Rh CE/D, occurs late in development and is expressed abundantly and broadly in kidney and testis. In the kidney RhCG is localized to the apical cell membrane of the collecting duct. Rhbg and its human analog (RhBG) are expressed mainly in liver, skin and the kidney tubules. In the kidney collecting duct, Rhbg is localized to the basolateral membrane. Based on structural similarities to the methylammonium and ammonium permease/ammonium (MEP/Amt) transporters in yeast and their sequence homology, these proteins probably function as NH(4)(+) transporters. An initial study has indicated that RhAG or RhCG promote efflux of NH(4)(+), whereas another study has suggested that RhAG functions as an NH(4)(+)-H(+) exchanger. Evidence for such a function is still circumstantial and data indicating that Rh proteins function as NH(4)(+) transporters are indirect.
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PMID:Non-erythroid Rh glycoproteins: a putative new family of mammalian ammonium transporters. 1292 May 97


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