A role for band 4.2 in human erythrocyte band 3 mediated anion transport

Malik, Saira; Sami, Malkit; Watts, Anthony

doi:10.1021/bi00089a024

Cited by 24 publications

(10 citation statements)

References 36 publications

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“…One study reported co-expression of protein 4.2 in Xenopus oocytes to increase AE1-mediated anion-exchange activity, 58 but contradictory results were observed in reconstituted proteoliposomes. 59 The protein kanadaptin was identified through a yeast two-hybrid screen as a binding partner of kAE1. 60 However, later investigation showed that kanadaptin is found in nuclei and mitochondria and that it does not co-localize with kAE1.…”

Section: Amino-terminal Domainmentioning

confidence: 99%

Defects in processing and trafficking of the AE1 Cl - /HCO3 - exchanger associated with inherited distal renal tubular acidosis

Shayakul

Alper

2004

Clinical and Experimental Nephrology

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Distal renal tubular acidosis (dRTA) results from impaired urinary acidification by the renal collecting duct. Acquired dRTA can be secondary to diverse pathological processes, including diabetic, ischemic, fibrosing, or immunological processes; less frequently it presents as a familial disorder with either an autosomal recessive or dominant pattern of transmission. Mutations in the SLC4A1/AE1/band 3 Cl(-)/HCO(3)(-) exchanger gene have been identified as causes for both dominant and recessive forms of dRTA. These mutations comprise a group almost entirely distinct from the SLC4A1 mutations that underlie the familial hemolytic anemia of hereditary spherocytosis. Why does one group of mutations express almost exclusively an isolated erythroid phenotype, whereas the second group of mutations expresses almost exclusively a phenotype explicable entirely by defective function of renal collecting duct type A intercalated cells? This review summarizes current research addressing this central question in the pathobiology of inherited dRTA associated with mutations in the SLC4A1 gene. Studying dRTA-associated mutant AE1 polypeptides can provide novel insights into the biology of the intercalated cell and the collecting duct as well as more generally into mechanisms by which epithelial cells generate and maintain functional polarity.

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Section: Amino-terminal Domainmentioning

confidence: 99%

Defects in processing and trafficking of the AE1 Cl - /HCO3 - exchanger associated with inherited distal renal tubular acidosis

Shayakul

Alper

2004

Clinical and Experimental Nephrology

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“…The functional significance of the association of protein 4.2 with band 3 in RBCs is currently unclear. In liposomes containing reconstituted band 3, anion transport activity decreased in the presence of increasing amounts of protein 4.2, 11 which suggested that protein 4.2 was a negative modulator of band-3 anion exchange activity. However, band-3-mediated anion transport activity has been reported to be unaffected 12 or increased 13 in human RBCs with protein-4.2 deficiency.…”

Section: Introductionmentioning

confidence: 99%

Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia

Toye

Ghosh

Young

et al. 2005

Blood

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IntroductionProtein 4.2 is a major constituent of the red blood cell (RBC) membrane skeletal network, present at about 200 000 copies per RBC. 1 The protein-4.2 gene EPB42 contains 13 exons. 2,3 There are two isoforms of protein 4.2, a minor 74-kDa isoform obtained when all these exons of the gene are expressed and a 72-kDa major isoform of protein 4.2 that lacks 30 of the 33 amino acids that are encoded by exon 1. 4,5 The exact role of protein 4.2 in RBCs has not been elucidated, but protein 4.2 binds to the N-terminal cytoplasmic domain of the band-3 anion exchanger (AE1) and also interacts with ankyrin in RBCs. 6,7 The presence of band 3 is critical for the stable incorporation of protein 4.2 into the RBC membrane, since human, 8 mouse, 9 and cow 10 RBCs deficient in band 3 are also completely deficient in protein 4.2. The functional significance of the association of protein 4.2 with band 3 in RBCs is currently unclear. In liposomes containing reconstituted band 3, anion transport activity decreased in the presence of increasing amounts of protein 4.2, 11 which suggested that protein 4.2 was a negative modulator of band-3 anion exchange activity. However, band-3-mediated anion transport activity has been reported to be unaffected 12 or increased 13 in human RBCs with protein-4.2 deficiency. In contrast, the absence of protein 4.2 slightly decreased anion transport activity in protein-4.2-null mouse RBCs. 14 Protein 4.2 also associates with spectrin, 15,16 ankyrin, 7 and protein 4.1 7 in solution, although the significance of these associations in vivo has yet to be demonstrated. Recently, protein 4.2 has been shown to interact with CD47, which probably contributes to the anchoring of the Rh complex to the RBC skeleton. 17,18 Protein 4.2 can probably interact with the inner leaflet of the lipid bilayer since it is fatty acylated with myristoyl and palmitoyl chains. 19,20 The complete or nearly complete absence of protein 4.2 is associated with an atypical form of hereditary spherocytosis (HS), highlighting the important role 4.2 plays in maintaining the stability and flexibility of RBCs. To date, 9 protein-4.2 mutations have been found associated with HS. Five lead to the premature termination of translation. 17,[21][22][23][24] Other protein-4.2 variants result from missense mutations that yield amino acid substitutions: protein 4.2 Nippon (GCTϾACT; A142T 25 ; occurs sporadically in the Japanese population and has been encountered once in whites), 26 protein 4.2 Tozeur (CGAϾCAA; R310Q), 27 protein 4.2 Shiga (CGCϾTGC; R317C), 28 and protein 4.2 Komatsu (GATϾTAT; D175Y). 29 Although there is a strict correlation between the occurrence of HS and the presence of these mutations (in homozygous or compound heterozygous states), the fact that these mutations are the direct cause of the absence of protein 4.2 has not been formally established. One possibility is that these point mutations affect the binding of protein 4.2 to band 3 and therefore its function. This has proved difficult to study using biochemical We h...

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“…Because the number of copies of band 4.2 on the erythrocyte membrane equals or exceeds that of the major structural proteins of the membrane skeleton, it is likely that band 4.2 plays an important role in membrane function or structure [14]. Recently, Malik et al [36] studied, in vitro, the effect on anion transport activity of increasing amounts of band 4.2 complexed with purified band 3 reconstituted into liposomes. Using this model, the authors showed an inverse correlation between sulfate flux and band 4.2 protein content.…”

Section: Discussionmentioning

confidence: 99%

Membrane cation and anion transport activities in erythrocytes of hereditary spherocytosis: Effects of different membrane protein defects

et al. 1997

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Hereditary spherocytosis (HS) is due to different membrane protein defects (i.e., deficiency of spectrin and ankyrin, band 3, or band 4.2). In order to gain new insight into the relationships between band 3 function and proteins associated with the cytoskeleton, we studied erythrocyte anion transport activity in HS characterized by different membrane protein defects. Anion transport activity was increased in HS due to partial band 4.2 deficiency or to band 4.2 absence, while in HS associated with deficiency of spectrin + ankyrin or band 3, the anion transport results were normal or decreased, respectively. Moreover, since HS erythrocytes are characterized by an increased Na and a decreased K, we studied the principal membrane cation transport pathways. Activity of the Na/K pump was increased in all HS studied, while no changes in Na/K/2Cl cotransport and Na/Li exchange were evident between control and HS as well as between forms of HS associated with different membrane protein defects. K/Cl cotransport activity was decreased in all HS studied compared to normal red cells. In all HS, passive membrane permeability to Na and K was increased compared to normal erythrocytes. The increased Na and the low K content can be attributed to the abnormal membrane permeability to cations, which is not related to a specific membrane protein defect. Am.

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A role for band 4.2 in human erythrocyte band 3 mediated anion transport

Cited by 24 publications

References 36 publications

Defects in processing and trafficking of the AE1 Cl - /HCO3 - exchanger associated with inherited distal renal tubular acidosis

Defects in processing and trafficking of the AE1 Cl - /HCO3 - exchanger associated with inherited distal renal tubular acidosis

Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia

Membrane cation and anion transport activities in erythrocytes of hereditary spherocytosis: Effects of different membrane protein defects

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