cDNA cloning and localization of a band 3-related protein from ileum

Chow, Alice M.; Dobbins, John W.; Aronson, Peter S.; Igarashi, Peter

doi:10.1152/ajpgi.1992.263.3.g345

Cited by 41 publications

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“…Immunolocalization studies have shown that AE2 is present on apical membranes of villus and crypt enterocytes in ileum (16) and on basolateral membranes of gastric parietal cells (18). The variant that was cloned from ileum is AE2a (16), and previous Northern blot data (10) suggest that in ileum the level of AE2a mRNA is greater than that of AE2b, consistent with the possibility that AE2a is the apical exchanger in ileum. Likewise, AE2b and AE2c mRNAs are abundant in stomach, suggesting that one or both of these variants might mediate Cl Ϫ /HCO 3 Ϫ exchange across the basolateral membrane of the parietal cell.…”

Section: Ae2 CL ϫ /Hcomentioning

confidence: 68%

“…In stomach, AE2 is expressed at high levels on the basolateral membrane of gastric parietal cells (18), where it presumably mediates the exchange of Cl Ϫ and HCO 3 Ϫ that occurs during acid secretion across the apical membrane. In small intestine, it has been localized on the apical membranes of both villus and crypt enterocytes in ileum (16), consistent with a role in both NaCl absorption and HCO 3 Ϫ secretion. The mechanisms underlying the large variations in AE2 mRNA expression levels in different tissues and the mechanisms by which the protein is localized to either apical or basolateral membranes are unknown.…”

mentioning

confidence: 68%

“…An increase in cAMP is known to inhibit the absorption of NaCl across the apical membranes of intestinal epithelial cells (30). This process involves the coupled activities of a Cl Ϫ /HCO 3 Ϫ exchanger, which appears to be the AE2a variant (16), and a Na ϩ /H ϩ exchanger (16) that is thought to be NHE3 (31). Although we are unaware of any evidence demonstrating that cAMP causes a direct inhibition of AE2 in intestine, cAMP has been shown to inhibit Cl Ϫ /HCO 3 Ϫ exchange in osteoblasts (32).…”

Section: Ae2 CL ϫ /Hcomentioning

confidence: 94%

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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: Ae2 CL ϫ /Hcomentioning

confidence: 68%

mentioning

confidence: 68%

Section: Ae2 CL ϫ /Hcomentioning

confidence: 94%

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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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“…Recently, the molecular cloning of the human AE2 gene has been reported (Medina et al 1997). Expression of the AE2 gene (detected by Northern blotting, immunoblotting, or immunocytochemistry) has been reported in a variety of mammalian organs, such as choroid plexus, stomach, ileum, kidney, testis, cochlea, salivary gland, and liver (Alper et al 1988;Kudrycki et al 1990;Lindsey et al 1990;Chow et al 1992;Parkkila et al 1993;Jons et al 1994;Brosius et al 1995;Negrini et al 1995;Vµzquez et al 1995), in some of which the expressed protein might have a role in hydroionic fluxes into secretions. AE3 and AE3 isoforms appear to be expressed mainly in excitable tissues of the nervous system and in cardiac muscle Kudrycki et al 1990;Linn et al 1992Linn et al , 1995Yannoukakos et al 1994).…”

Section: Introductionmentioning

confidence: 99%

In situ detection of AE2 anion-exchanger mRNA in the human liver

García

Montuenga

Medina

et al. 1998

Cell and Tissue Research

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Na + -independent anion exchangers, a family of membrane proteins that mediate electroneutral exchanges of chloride and bicarbonate ions across the cell membrane, are considered to be involved in intracellular pH regulation as well as in transepithelial acid/base transport. Previous immunohistochemical data have shown that anion-exchanger-2 (AE2) protein is expressed in the liver parenchyma, localizing at both the canaliculi and the luminal surfaces of intrahepatic bile ducts, where it may have a role in the biliary secretion of bicarbonate. In the present study, we have carried out in situ hybridization experiments on biopsies of human liver using three overlapping antisense anion-exchanger-2 riboprobes. Anion-exchanger-2 mRNA signals were localized mainly in the cytoplasm of terminal and interlobular bile-duct cells, whereas weaker signals were observed in bile-duct cells of larger intrahepatic ducts. Furthermore, some hepatocytes, mostly periportal, contained detectable anion-exchanger-2 mRNA signals in their cytoplasm. No hybridization signals were observed in controls with sense riboprobes, with omission of the antisense probe, or with treatment of the sections with RNase before hybridizations. Finally, intense anion-exchanger-2 hybridization signals were observed in lymphomononuclear cells in sinusoids and in portal infiltrates. Immunocytochemical data from reverse-phase sections suggest that these cells correspond to some of the CD45R+ (UCHL1+) T lymphocytes resident in the liver.

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“…an I → N substitution in a highly conserved position (783) at the terminal boundary of TM11. Alignment of the 13 known sequences pertaining to different members of the AE1, AE2, AE3 families (Chow et al, 1992;Wood, 1992;Yannoukakos et al, 1994;Kay et al, 1995) revealed that the isoleucine 783 is perfectly conserved through evolution, suggesting that this residue is critical for transmembrane domain structure. Ten other substitutions of conserved residues have been described in association with band 3 deficiency (Alloisio et al, 1993;Jarolim et al, 1994aJarolim et al, , 1995Maillet et al, 1995;Eber et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Novel band 3 variants (bands 3 Foggia, Napoli I and Napoli II) associated with hereditary spherocytosis and band 3 deficiency: status of the D38A polymorphism within the EPB3 locus

et al. 1997

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Summary.We report three novel variants of band 3 associated with hereditary spherocytosis: band 3 Foggia (311delC; ACCCAC → ACCAC), band 3 Napoli I (447insT; TCT → TTCT) and band 3 Napoli II (I783N; ATC → AAC). The first two mutations resulted in premature termination of translation, making one haploid set of band 3 mRNA unavailable. Since it affected a highly conserved position at the terminal end of transmembrane domain 11, the third mutation prevented one haploid set of band 3 from becoming incorporated or stabilized into the membrane. These three mutations resulted in a reduction of the band 3 level in the red cell membrane (by 20-25%) and were dominantly transmitted. The D38A substitution (GAC → GCC) is a low frequency change of band 3. In one compound heterozygote D38A/Napoli II, a markedly aggravated picture required early splenectomy. In contrast, the D38A change was not associated with deterioration in another compound heterozygote, carrying in trans, the previously recorded R760W mutation (CGG → TGG). In the aggravated case, SSCP analysis did not exhibit any additional change in the two EPB3 alleles. Nor did it show any alteration in the exons of the two ANK1 alleles, and the aggravating factor remained elusive. The D38A alteration should be regarded as an innocuous polymorphism.Keywords: hereditary spherocytosis, band 3, EPB3 gene, mutations, polymorphism.Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia characterized by spheroidal, osmotically fragile, erythrocytes (for review, see Lux & Palek, 1995). The primary molecular defect can reside in several red cell membrane structural proteins: spectrin, ankyrin, band 3 and protein 4.2. Band 3, or the anion exchanger 1 (AE1), is the most abundant protein of the red cell membrane (1 : 2 × 10 6 monomers per cell) and consists of two domains with distinct functions (for review, see Tanner, 1993). The cytoplasmic domain (residues 1-403) binds a number of proteins including ankyrin and protein 4.2. The membrane domain (residues 404-883) harbours 14 membrane-spanning segments (TM) and mediates chloride-bicarbonate passive antiport. Band 3 cDNA has been entirely sequenced (Tanner et al, 1988;Lux et al, 1989;Schofield et al, 1994), and the structure of the band 3 gene (EPB3) has been determined (Schofield et al, 1994;Sahr et al, 1994). Approximately 20% of HS cases are associated with a substantial reduction of the band 3 amount in the red cell membrane (20-40%). Basically, their inheritance pattern is autosomal dominant and their clinical phenotype is mild to moderate in the heterozygous state. Band 3 deficiency is accompanied by a roughly proportional reduction in protein 4.2. Several mutations leading to band 3 reduction and HS have been recently identified. They include (i) mutations producing premature termination of translation (at any position along the whole coding sequence) and (ii) substitutions of highly conserved amino acids within the membrane domain, especially in the last membrane spanning segments (TM9-TM14) or at their bounda...

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cDNA cloning and localization of a band 3-related protein from ileum

Cited by 41 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

In situ detection of AE2 anion-exchanger mRNA in the human liver

Novel band 3 variants (bands 3 Foggia, Napoli I and Napoli II) associated with hereditary spherocytosis and band 3 deficiency: status of the D38A polymorphism within the EPB3 locus

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