Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes

Soleimani, Manoocher; Burnham, Charles E.

doi:10.1046/j.1523-1755.2000.00857.x

Cited by 74 publications

(70 citation statements)

References 67 publications

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“…These Ab's were raised against highly specific regions of human NBC-1 and are unlikely to recognize other Na + -dependent and Na + -independent HCO 3 -transport molecules cloned so far (12,27). Our results indicate that NBC-1 is present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium.…”

Section: Discussionmentioning

confidence: 78%

“…It is therefore possible that mutations in the common NBC-1 region may affect the properties of all these isoforms, resulting in renal and extrarenal manifestations. For example, because kNBC-1 is thought to be responsible for a majority of HCO 3 -reabsorption from renal proximal tubules (10)(11)(12), its inactivation can readily explain the occurrence of pRTA. Recent studies (13,14) suggest that NBC-1 may also play a significant role in HCO 3 -transport by the corneal endothelium, which potentially could explain the occurrence of band keratopathy (4).…”

Section: Introductionmentioning

confidence: 99%

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Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis

Usui¹,

Hara²,

Satoh³

et al. 2001

J. Clin. Invest.

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Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the Na + -HCO 3 -cotransporter (NBC-1). However, the mechanism by which NBC-1 inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters are present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium. In the human lens epithelial (HLE) cells, RT-PCR detected mRNAs of both kNBC-1 and pNBC-1. Although a Na + -HCO 3 -cotransport activity has not been detected in mammalian lens epithelia, cell pH (pH i ) measurements revealed the presence of Cl --independent, electrogenic Na + -HCO 3 -cotransport activity in HLE cells. In addition, up to 80% of amiloride-insensitive pH i recovery from acid load in the presence of HCO 3 -/CO 2 was inhibited by adenovirus-mediated transfer of a specific hammerhead ribozyme against NBC-1, consistent with a major role of NBC-1 in overall HCO 3 -transport by the lens epithelium. These results indicate that the normal transport activity of NBC-1 is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis

Usui¹,

Hara²,

Satoh³

et al. 2001

J. Clin. Invest.

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“…The functional family of HCO 3 Ϫ transporters includes Cl Ϫ / HCO 3 Ϫ exchangers, three Na ϩ /HCO 3 Ϫ co-transporters, and K ϩ / HCO 3 Ϫ co-transporter (32,33). These transporters are much larger than SbtA, and there was no similarity in amino acid sequences between SbtA and mammalian-type HCO 3 Ϫ transporters.…”

Section: Fig 6 Phylogenetic Trees Of Sbta (A) and Ntpj (B)mentioning

confidence: 99%

Genes Essential to Sodium-dependent Bicarbonate Transport in Cyanobacteria

Shibata¹,

Katoh²,

Sonoda³

et al. 2002

Journal of Biological Chemistry

258

220

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The cyanobacterium Synechocystis sp. strain PCC 6803 possesses two CO 2 uptake systems and two HCO 3 ؊ transporters. We transformed a mutant impaired in CO 2 uptake and in cmpA-D encoding a HCO 3 ؊ transporter with a transposon inactivation library, and we recovered mutants unable to take up HCO 3 ؊ and grow in low CO 2 at pH 9.0. They are all tagged within slr1512 (designated sbtA). We show that SbtA-mediated transport is induced by low CO 2 , requires Na ؉ , and plays the major role in HCO 3 ؊ uptake in Synechocystis. Inactivation of slr1509 (homologous to ntpJ encoding a Na ؉ /K ؉ -translocating protein) abolished the ability of cells to grow at [Na ؉ ] higher than 100 mM and severely depressed the activity of the SbtA-mediated HCO 3 ؊ transport. We propose that the SbtA-mediated HCO 3 ؊ transport is driven by ⌬Na ؉ across the plasma membrane, which is disrupted by inactivating ntpJ. Phylogenetic analyses indicated that two types of sbtA exist in various cyanobacterial strains, all of which possess ntpJ. The sbtA gene is the first one identified as essential to Na ؉ -dependent HCO 3 ؊ transport in photosynthetic organisms and may play a crucial role in carbon acquisition when CO 2 supply is limited, or in Prochlorococcus strains that do not possess CO 2 uptake systems or Cmp-dependent HCO 3 ؊ transport.Growth of many photosynthetic microorganisms depends on the activity of a CO 2 -concentrating mechanism (CCM), 1 which raises the [CO 2 ] in close proximity to ribulose-1,5-bisphosphate carboxylase/oxygenase and thereby enables efficient CO 2 fixation despite the low affinity of the enzyme for CO 2 (1, 2). In the cyanobacterium Synechocystis sp. strain PCC 6803 (hereafter Synechocystis 6803), the CCM involves active CO 2 uptake and HCO 3 Ϫ transport. We have recently identified two systems for CO 2 uptake in Synechocystis 6803, one constitutive and the other inducible by low CO 2 (3). As deduced from phylogenetic analysis of proteins encoded by the genes involved, these CO 2 uptake systems are present in various cyanobacteria with the exception of Prochlorococcus marinus (3). The inducible system that depends on NdhD3/ NdhF3/CupA shows higher maximal activity and higher affinity for CO 2 than the constitutive, NdhD4/NdhF4/CupB-dependent system. Inactivation of two different genes, one encoding a component of the constitutive system and the other a constituent of the inducible system, abolished CO 2 uptake activity. The double mutants were unable to grow at pH 7.0 under air level of CO 2 (3, 4). In contrast, because the mutants possessed HCO 3 Ϫ transport capability, they could grow like the wild type (WT) at pH 9.0 in air.An ABC-type HCO 3 Ϫ transporter encoded by cmpABCD has been identified in Synechococcus sp. strain PCC 7942 (thereafter Synechococcus 7942) (5). Inactivation of cmp genes in Synechocystis 6803, however, had little effect on the HCO 3 Ϫ transport activity. This indicated that another HCO 3 Ϫ transporter, as yet unidentified, plays a central role in HCO 3 Ϫ uptake. Sodium ions are essential for ...

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“…The first is a new member of the AE family, named AE4 (38). AE4 was cloned from isolated rabbit ␤-intercalated cells and was shown to function as a Na ϩ -independent Cl Ϫ / HCO 3 Ϫ exchanger, although it has higher homology to members of the Na ϩ -HCO 3 Ϫ cotransporter (NBC) family (27,33) than to the SLC4 family. Important features of AE4 reported in the study of Tsuganezawa et al (38) are the resistance to DIDS when expressed in Xenopus oocytes and the colocalization of AE4 and peanut lectin in the luminal membrane of the rabbit CCD.…”

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confidence: 99%

AE4 is a DIDS-sensitive Cl⁻/HCO 3 − exchanger in the basolateral membrane of the renal CCD and the SMG duct

Ko¹,

Luo²,

Hager

et al. 2002

American Journal of Physiology-Cell Physiology

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Ϫ exchange. The identity of the luminal exchanger is a matter of debate. Anion exchanger isoform 4 (AE4) cloned from the rabbit kidney was proposed to perform this function (Tsuganezawa H et al. J Biol Chem 276: 8180-8189, 2001). By contrast, it was proposed (Royaux IE et al. Proc Natl Acad Sci USA 98: 4221-4226, 2001) that pendrin accomplishes this function in the mouse CCD. In the present work, we cloned, localized, and characterized the function of the rat AE4. Northern blot and RT-PCR showed high levels of AE4 mRNA in the CCD. Expression in HEK-293 and LLC-PK1 cells showed that AE4 is targeted to the plasma membrane. Measurement of intracellular pH (pHi) revealed that AE4 indeed functions as a Cl Ϫ /HCO 3 Ϫ exchanger. However, AE4 activity was inhibited by DIDS. Immunolocalization revealed species-specific expression of AE4. In the rat and mouse CCD and the mouse SMG duct AE4 was in the basolateral membrane. By contrast, in the rabbit, AE4 was in the luminal and lateral membranes. In both, the rat and rabbit CCD AE4 was in ␣-intercalated cells. Importantly, localization of AE4 was not affected by the systemic acid-base status of the rats. Therefore, we conclude that expression and possibly function of AE4 is species specific. In the rat and mouse AE4 functions as a Cl

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Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes

Cited by 74 publications

References 67 publications

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis

Genes Essential to Sodium-dependent Bicarbonate Transport in Cyanobacteria

AE4 is a DIDS-sensitive Cl⁻/HCO 3 − exchanger in the basolateral membrane of the renal CCD and the SMG duct

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Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes

Cited by 74 publications

References 67 publications

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis

Genes Essential to Sodium-dependent Bicarbonate Transport in Cyanobacteria

AE4 is a DIDS-sensitive Cl−/HCO 3 − exchanger in the basolateral membrane of the renal CCD and the SMG duct

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AE4 is a DIDS-sensitive Cl⁻/HCO 3 − exchanger in the basolateral membrane of the renal CCD and the SMG duct