Substrate-dependent Interference of Carbonic Anhydrases with the Glutamine Transporter SNAT3-Induced Conductance

Weise, Alexandra; Schneider, Hans‐Peter; McKenna, Robert; Deitmer, Joachim W.

doi:10.1159/000325208

Cited by 4 publications

(2 citation statements)

References 58 publications

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“…in mass spectrometry. Recently, the membrane conductance associated with the glutamine transporter SNAT3 (SLC38A3) was shown to be suppressed not only by CAII activity [52], but also by CAI and CAIII [53].…”

Section: Discussionmentioning

confidence: 99%

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

et al. 2011

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Transport metabolons have been discussed between carbonic anhydrase II (CAII) and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1), to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 µM), while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity.

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Section: Discussionmentioning

confidence: 99%

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

et al. 2011

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“…This also compensates acidosis after breakdown of carbonic acid into H 2 O and CO 2 and release through the lungs. Notably, carbonic acid anhydrase interacts with SNAT3, providing a link between removal of HCO 3 − and glutamine transport [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression

Balkrishna

Welford²,

Hatzoglou

et al. 2014

Cell Physiol Biochem

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Background: Despite homeostatic pH regulation, systemic and cellular pH changes take place and strongly influence metabolic processes. Transcription of the glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammonia production. Methods: Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values. Results: Up-regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and by the up-regulation of gene transcription. Stabilisation of the mRNA involved a pH-response element, while enhanced transcription made use of a second pH-sensitive Sp1 binding site in addition to a constitutive Sp1 binding site. Transcriptional regulation dominated the early response to acidosis, while mRNA stability was more important for chronic adaptation. Tissue-specific expression of SNAT3, by contrast, appeared to be controlled by promoter methylation and histone modifications. Conclusions: Regulation of SNAT3 gene expression by extracellular pH involves post-transcriptional and transcriptional mechanisms, the latter being distinct from the mechanisms that control the tissue-specific expression of the gene.

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Carbonic Anhydrases and Their Interplay with Acid/Base-Coupled Membrane Transporters

Becker

Klier

Deitmer

2013

Subcellular Biochemistry

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Carbonic anhydrases (CAs) have not only been identified as ubiquitous enzymes catalyzing the fast reversible hydration of carbon dioxide to generate or consume protons and bicarbonate, but also as intra- and extracellular proteins, which facilitate transport function of many acid/base transporting membrane proteins, coined 'transport metabolon'. Functional interaction between CAs and acid/base transporters, such as chloride/bicarbonate exchanger (AE), sodium-bicarbonate cotransporter (NBC) and sodium/hydrogen exchanger (NHE) has been shown to require both catalytic CA activity as well as direct binding of the enzyme to specific sites on the transporter. In contrast, functional interaction between different CA isoforms and lactate-proton-cotransporting monocarboxylate transporters (MCT) has been found to be isoform-specific and independent of CA catalytic activity, but seems to require an intramolecular proton shuttle within the enzyme. In this chapter, we review the various types of interactions between acid/base-coupled membrane carriers and different CA isoforms, as studied in vitro, in intact Xenopus oocytes, and in various mammalian cell types. Furthermore, we discuss recent findings that indicate the significance of these 'transport metabolons' for normal cell functions.

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Substrate-dependent Interference of Carbonic Anhydrases with the Glutamine Transporter SNAT3-Induced Conductance

Cited by 4 publications

References 58 publications

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression

Carbonic Anhydrases and Their Interplay with Acid/Base-Coupled Membrane Transporters

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