Evidence for Up-regulation of the Endogenous Na-K-2Cl Co-transporter by Molecular Interactions with the Anion Exchanger tAE1 Expressed in Xenopus Oocyte

Guizouarn, Hélène; Gabillat, Nicole; Borgèse, Franck

doi:10.1074/jbc.m311920200

Cited by 11 publications

(8 citation statements)

References 37 publications

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“…21 In the past, expression studies of different channels or membrane proteins in xenopus oocytes have demonstrated the relevance of interactions between studied proteins and oocyte endogenous transporters. [22][23][24][25][26] However, the present data disagree with this interpretation. Only specific point mutations are able to confer to hAE1 the possibility to enhance a putative endogenous cation conductance; the wild-type hAE1 is not able to stimulate any cation conductance in oocyte (Figure 2).…”

Section: Discussioncontrasting

confidence: 56%

Point mutations involved in red cell stomatocytosis convert the electroneutral anion exchanger 1 to a nonselective cation conductance

Guizouarn

Martial

Gabillat

et al. 2007

Blood

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The anion exchanger 1 (AE1) is encoded by the SLC4A1 gene and catalyzes the electroneutral anion exchange across cell plasma membrane. It is the most abundant transmembrane protein expressed in red cell where it is involved in CO 2 transport. Recently, 4 new point mutations of SLC4A1 gene have been described leading to missense mutations in the protein sequence (L687P, D705Y, S731P, or H734R). These point mutations were associated with hemolytic anemia, and it was shown that they confer a cation transport feature to the human AE1. Facing this unexpected property for an electroneutral anion exchanger, we have studied the transport features of mutated hAE1 by expression in xenopus oocytes. Our results show that the point mutations of hAE1 convert the electroneutral anion exchanger to a cation conductance: the exchangers are no longer able to exchange Cl ؊ and HCO 3 ؊ , whereas they transport Na ؉ and K ؉ through a conductive mechanism. These data shed new light on transport mechanisms showing the tiny difference, in terms of primary sequence, between an electroneutral exchange and a conductive pathway. (Blood.

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Section: Discussioncontrasting

confidence: 56%

Point mutations involved in red cell stomatocytosis convert the electroneutral anion exchanger 1 to a nonselective cation conductance

Guizouarn

Martial

Gabillat

et al. 2007

Blood

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“…These include, in addition to increased glyburide-and NPPB-sensitive anion conductance, increased permeability to the cations Na ϩ , K ϩ , and Li ϩ (24) and to the zwitterion taurine [both AE1-associated and endogenous in origin (18)], as well as secondary activation of endogenous oocyte NKCC activity (23). Similar changes in oocyte transport properties were associated with expression of a mutant human AE1 lacking transmembrane spans 6 and 7 (40).…”

Section: Discussionmentioning

confidence: 92%

The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes

Stewart

Vandorpe

Heneghan

et al. 2010

American Journal of Physiology-Cell Physiology

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The previously undescribed heterozygous missense mutation E758K was discovered in the human AE1/SLC4A1/band 3 gene in two unrelated patients with well-compensated hereditary spherostomatocytic anemia (HSt). Oocyte surface expression of AE1 E758K, in contrast to that of wild-type AE1, required coexpressed glycophorin A (GPA). The mutant polypeptide exhibited, in parallel, strong GPA dependence of DIDS-sensitive (36)Cl(-) influx, trans-anion-dependent (36)Cl(-) efflux, and Cl(-)/HCO(3)(-) exchange activities at near wild-type levels. AE1 E758K expression was also associated with GPA-dependent increases of DIDS-sensitive pH-independent SO(4)(2-) uptake and oxalate uptake with altered pH dependence. In marked contrast, the bumetanide- and ouabain-insensitive (86)Rb(+) influx associated with AE1 E758K expression was largely GPA-independent in Xenopus oocytes and completely GPA-independent in Ambystoma oocytes. AE1 E758K-associated currents in Xenopus oocytes also exhibited little or no GPA dependence. (86)Rb(+) influx was higher but inward cation current was lower in oocytes expressing AE1 E758K than previously reported in oocytes expressing the AE1 HSt mutants S731P and H734R. The pharmacological inhibition profile of AE1 E758K-associated (36)Cl(-) influx differed from that of AE1 E758K-associated (86)Rb(+) influx, as well as from that of wild-type AE1-mediated Cl(-) transport. Thus AE1 E758K-expressing oocytes displayed GPA-dependent surface polypeptide expression and anion transport, accompanied by substantially GPA-independent, pharmacologically distinct Rb(+) flux and by small, GPA-independent currents. The data strongly suggest that most of the increased cation transport associated with the novel HSt mutant AE1 E758K reflects activation of endogenous oocyte cation permeability pathways, rather than cation translocation through the mutant polypeptide.

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“…Similarly, mutated forms of band 3 (the chloride bicarbonate exchanger AE1) identified in cryohydrocytosis (CHC) with present stomatin (11) were also shown to convert AE1 into a cation channel (23). However, it has also been described that expression of trout anion exchanger 1 in Xenopus oocytes led to the stimulation of Na ϩ and Cl Ϫ influx, most likely mediated by endogenous Na-K-2Cl (NKCC) cotransporter (22). Moreover, recent results on CHC red cells suggested that cross-talk between the mutated band 3 and other transporters (KCC and KNHE) might also increase the cation permeability in cryohydrocytosis (6).…”

Section: Discussionmentioning

confidence: 95%

Human RhAG ammonia channel is impaired by the Phe65Ser mutation in overhydrated stomatocytic red cells

Genetet

Ripoche

Picot

et al. 2012

American Journal of Physiology-Cell Physiology

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In red cells, Rh-associated glycoprotein (RhAG) acts as an ammonia channel, as demonstrated by stopped-flow analysis of ghost intracellular pH (pH(i)) changes. Recently, overhydrated hereditary stomatocytosis (OHSt), a rare dominantly inherited hemolytic anemia, was found to be associated with a mutation (Phe65Ser or Ile61Arg) in RHAG. Ghosts from the erythrocytes of four of the OHSt patients with a Phe65Ser mutation were resealed with a pH-sensitive probe and submitted to ammonium gradients. Alkalinization rate constants, reflecting NH(3) transport through the channel and NH(3) diffusion unmediated by RhAG, were deduced from time courses of fluorescence changes. After subtraction of the constant value found for Rh(null) lacking RhAG, we observed that alkalinization rate constant values decreased ∼50% in OHSt compared with those of controls. Similar RhAG expression levels were found in control and OHSt. Since half of the expressed RhAG in OHSt most probably corresponds to the mutated form of RhAG, as expected from the OHSt heterozygous status, this dramatic decrease can be therefore related to the loss of function of the Phe65Ser-mutated RhAG monomer.

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Evidence for Up-regulation of the Endogenous Na-K-2Cl Co-transporter by Molecular Interactions with the Anion Exchanger tAE1 Expressed in Xenopus Oocyte

Cited by 11 publications

References 37 publications

Point mutations involved in red cell stomatocytosis convert the electroneutral anion exchanger 1 to a nonselective cation conductance

Point mutations involved in red cell stomatocytosis convert the electroneutral anion exchanger 1 to a nonselective cation conductance

The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes

Human RhAG ammonia channel is impaired by the Phe65Ser mutation in overhydrated stomatocytic red cells

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