Anion exchanger 1 in human kidney and oncocytoma differs from erythroid AE1 in its NH2 terminus

Kollert-Jons, A.; Wagner, Silvia; Hübner, Stefan; Appelhans, Heribert; Drenckhahn, D.

doi:10.1152/ajprenal.1993.265.6.f813

Cited by 74 publications

(78 citation statements)

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“…The 270-amino acid sequence that is eliminated contains a histidine-rich domain, numerous proline-rich regions, and domains consisting of stretches of acidic or basic residues that have counterparts in AE2a (10, 14). Transcription from the AE2c promoter leads to production of an mRNA encoding an N-terminal truncated (4,7,19); AE1k1, kidney AE1 mRNA with alternative first exon spliced to exon 4, corresponding to mouse and human kidney mRNAs and a minor rat kidney mRNA (5,7,8); AE1k2, major rat kidney mRNA in which intron 3 sequences are retained (5, 7). AE3b, mRNA encoding brain form of AE3, which is also expressed in some other tissues (9, 10); AE3c, mRNA encoding cardiac form of AE3 (11)(12)(13).…”

Section: Use Of Alternative Promoters Leads To Tissue-specific Expresmentioning

confidence: 99%

“…[1][2][3]. The AE1 gene encodes both erythrocyte band 3 (4) and kidney band 3 (5)(6)(7)(8), an N-terminal truncated variant of the exchanger. Kidney AE1 mRNA is transcribed from an alternative promoter located in the third intron of the erythrocyte transcription unit (7), and utilizes a Met codon in exon 5 as the translation start site (7,8).…”

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confidence: 99%

“…The AE1 gene encodes both erythrocyte band 3 (4) and kidney band 3 (5)(6)(7)(8), an N-terminal truncated variant of the exchanger. Kidney AE1 mRNA is transcribed from an alternative promoter located in the third intron of the erythrocyte transcription unit (7), and utilizes a Met codon in exon 5 as the translation start site (7,8). In the case of AE3, a 4.4-kb mRNA encoding a 1227-amino acid variant is expressed in brain and several other tissues (9,10), and a 3.8-kb mRNA is expressed in heart (9 -13).…”

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confidence: 99%

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Three N-terminal Variants of the AE2 Cl-/HCO3- Exchanger Are Encoded by mRNAs Transcribed from Alternative Promoters

Wang¹,

Schultheis

Shull

1996

Journal of Biological Chemistry

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Multiple AE2 Cl ؊ /HCO 3 ؊ exchanger mRNAs have been identified in rat. To determine the genetic basis for these mRNAs and whether they encode different variants of the exchanger, we used both rapid amplification of cDNA ends and S1 nuclease protection protocols and examined the organization of the gene. mRNAs encoding three N-terminal variants of AE2 (AE2a, AE2b, and AE2c) were identified and shown to be transcribed from alternative promoters. The AE2a transcription unit consists of 23 exons, with exons 1 and 2 containing 5 -untranslated sequence and the first 17 codons. The first exon of AE2b is located in intron 2; it contains 5 -untranslated sequence and an alternative 3-amino acid Nterminal coding sequence and is spliced to exon 3. The first exon of AE2c is located in intron 5; it consists of 5 -untranslated sequence and is spliced to exon 6, which contains the translation initiation codon corresponding to Met-200 of AE2a. Northern analysis shows that AE2a is expressed in all tissues, AE2b exhibits a more restricted distribution with highest levels in stomach, and AE2c is expressed only in stomach. Thus, the use of alternative promoters leads to the production of three N-terminal variants of AE2 that exhibit tissue-specific patterns of expression.

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Section: Use Of Alternative Promoters Leads To Tissue-specific Expresmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Three N-terminal Variants of the AE2 Cl-/HCO3- Exchanger Are Encoded by mRNAs Transcribed from Alternative Promoters

Wang¹,

Schultheis

Shull

1996

Journal of Biological Chemistry

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“…The protein terminates with a cytoplasmic 33-amino acid carboxyl-terminal domain (8,9). A truncated form of human AE1 beginning at methionine 66 is found in kidney (10). Other plasma membrane anion exchange proteins include AE2 and AE3 and recently identified AE4, DRA (down-regulated in adenoma), and Pendrin (11)(12)(13)(14)(15)(16).…”

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confidence: 99%

A Transport Metabolon

Sterling

Reithmeier

Casey

2001

Journal of Biological Chemistry

334

153

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The cytoplasmic carboxyl-terminal domain of AE1, the plasma membrane chloride/bicarbonate exchanger of erythrocytes, contains a binding site for carbonic anhydrase II (CAII). To examine the physiological role of the AE1/CAII interaction, anion exchange activity of transfected HEK293 cells was monitored by following the changes in intracellular pH associated with AE1-mediated bicarbonate transport. AE1-mediated chloride/bicarbonate exchange was reduced 50 -60% by inhibition of endogenous carbonic anhydrase with acetazolamide, which indicates that CAII activity is required for full anion transport activity. AE1 mutants, unable to bind CAII, had significantly lower transport activity than wild-type AE1 (10% of wild-type activity), suggesting that a direct interaction was required. To determine the effect of displacement of endogenous wild-type CAII from its binding site on AE1, AE1-transfected HEK293 cells were co-transfected with cDNA for a functionally inactive CAII mutant, V143Y. AE1 activity was maximally inhibited 61 ؎ 4% in the presence of V143Y CAII. A similar effect of V143Y CAII was found for AE2 and AE3cardiac anion exchanger isoforms. We conclude that the binding of CAII to the AE1 carboxyl-terminus potentiates anion transport activity and allows for maximal transport. The interaction of CAII with AE1 forms a transport metabolon, a membrane protein complex involved in regulation of bicarbonate metabolism and transport.Carbon dioxide, the metabolic end product of oxidative respiration, must be effectively cleared from the human body. CO 2 diffuses out of cells into the blood stream and into erythrocytes, where it is hydrated by cytosolic carbonic anhydrase (CA). 1 The resulting membrane-impermeant HCO 3 Ϫ is exported into the plasma by the plasma membrane Cl Ϫ /HCO 3 Ϫ anion exchanger (AE1), thus increasing the blood capacity for carrying CO 2 . Upon returning to the lungs the process is reversed; HCO 3 Ϫ is transported into the erythrocyte in exchange for Cl Ϫ by AE1 and dehydrated by CA, and the resulting CO 2 diffuses across the erythrocyte and alveolar membranes to be expired from the body. The 5 ϫ 10 4 s Ϫ1 turnover rate of AE1 (1) and the high content of AE1 in the membrane (2) facilitate completion of bicarbonate transport within 50 ms during passage of an erythrocyte through a capillary (3).AE1 is a 911-amino acid polytopic glycoprotein that facilitates the one for one electroneutral exchange of Cl Ϫ for HCO 3

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“…Kidney AE1 is located on the basolateral membrane of acid-secreting a-intercalated cells of the distal tubule and collecting duct of the nephron and is identical to eAE1 except that transcription of kAE1 occurs from an alternative initiation site within intron 3 leading to a protein with a truncated N-terminus. Mouse kAE1 lacks 79 N-terminal amino acid residues and human kAE1 65, because of which kAE1 no longer binds to ankyrin, protein 4.1, or glycolytic enzymes (Drenckhahn and Merte, 1987;Brosius et al, 1989;Kollert-Jons et al, 1993;Zhang et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the interaction between human kidney anion exchanger 1 and kanadaptin using yeast two-hybrid systems

et al. 2006

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Kidney anion exchanger adaptor protein (Kanadaptin) is a protein which interacts with the cytoplasmic N-terminal domain of kidney anion exchanger 1 (kAE1) and was first detected in mice using the yeast two-hybrid system and was also found to co-localize with kAE1 in rabbit a-intercalated cells. Impaired trafficking of human kAE1 can result in the kidney disease-distal renal tubular acidosis (dRTA), and defective interaction between human kAE1 and kanadaptin may cause this trafficking impairment and be the basis for dRTA pathogenesis. However, it is unknown whether kAE1 can really interact with kanadaptin in humans. We have thus investigated the interaction between human kAE1 and human kanadaptin by using both Gal4 and LexA yeast two-hybrid systems. It was found that co-expression of Gal4DBD fused to the cytoplasmic N-terminal domain of kAE1 and Gal4AD fused to kanadaptin could not activate the transcription of the ADE2, HIS3 and lacZ reporters in the Gal4 system. A similar result was obtained for the interaction between B42AD fused to the cytoplasmic N-terminal domain of kAE1 and LexA fused to kanadaptin in activation of lacZ transcription in the LexA system. The absence of interaction between the fusion proteins in both yeast two-hybrid systems raises the possibility that kAE1 may not interact with kanadaptin in human cells. Considerably different structures of both kAE1 and kanadaptin in mice and humans may lead to different binding properties of the proteins in these two species.

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Anion exchanger 1 in human kidney and oncocytoma differs from erythroid AE1 in its NH2 terminus

Cited by 74 publications

References 0 publications

Three N-terminal Variants of the AE2 Cl-/HCO3- Exchanger Are Encoded by mRNAs Transcribed from Alternative Promoters

Three N-terminal Variants of the AE2 Cl-/HCO3- Exchanger Are Encoded by mRNAs Transcribed from Alternative Promoters

A Transport Metabolon

Analysis of the interaction between human kidney anion exchanger 1 and kanadaptin using yeast two-hybrid systems

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