The SLC12 family of electroneutral cation-coupled chloride cotransporters

Arroyo, Juan Pablo; Kahle, Kristopher T.; Gamba, Gerardo

doi:10.1016/j.mam.2012.05.002

Cited by 135 publications

(123 citation statements)

References 68 publications

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“…The SLC12 family is composed of nine genes encoding seven functionally identified members and two orphan transporters (4,38,55). The family is divided into two branches based on the degree of identity: one branch encodes the Na ϩ -dependent Na-K-2Cl cotransporters (NKCC1 and NKCC2) and the Na-Cl cotransporter (NCC).…”

Section: Slc12 Familymentioning

confidence: 99%

“…All these proteins are expressed in the kidney, with the exception of KCC2, which is neuron-specific (98). Two additional members, CCC8 and CCC9, exhibit a low degree of identity with other members, and their physiological functions are not yet understood (4,53).…”

Section: Slc12 Familymentioning

confidence: 99%

“…An important characteristic of the SLC12 family is that the activity of all members is regulated by the phosphorylation/ dephosphorylation of key serine/threonine residues located at the amino-and carboxy-terminal domains (4,38). Interestingly, the phosphorylated residues differ between the two branches.…”

Section: Slc12 Familymentioning

confidence: 99%

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Physiological role of SLC12 family members in the kidney

Bazúa‐Valenti

Castañeda‐Bueno

Gamba

2016

American Journal of Physiology-Renal Physiology

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The solute carrier family 12, as numbered according to Human Genome Organisation (HUGO) nomenclature, encodes the electroneutral cation-coupled chloride cotransporters that are expressed in many cells and tissues; they play key roles in important physiological events, such as cell volume regulation, modulation of the intracellular chloride concentration, and transepithelial ion transport. Most of these family members are expressed in specific regions of the nephron. The Na-K-2Cl cotransporter NKCC2, which is located in the thick ascending limb, and the Na-Cl cotransporter, which is located in the distal convoluted tubule, play important roles in salt reabsorption and serve as the receptors for loop and thiazide diuretics, respectively (Thiazide diuretics are among the most commonly prescribed drugs in the world.). The activity of these transporters correlates with blood pressure levels; thus, their regulation has been a subject of intense research for more than a decade. The K-Cl cotransporters KCC1, KCC3, and KCC4 are expressed in several nephron segments, and their role in renal physiology is less understood but nevertheless important. Evidence suggests that they are involved in modulating proximal tubule glucose reabsorption, thick ascending limb salt reabsorption and collecting duct proton secretion. In this work, we present an overview of the physiological roles of these transporters in the kidney, with particular emphasis on the knowledge gained in the past few years.

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Section: Slc12 Familymentioning

confidence: 99%

Section: Slc12 Familymentioning

confidence: 99%

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Physiological role of SLC12 family members in the kidney

Bazúa‐Valenti

Castañeda‐Bueno

Gamba

2016

American Journal of Physiology-Renal Physiology

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“…Distribution of the genes in which at least a single nucleotide polymorphism was detected (considering only the coding regions) in the different chromosomes (in blue) compared to the number of annotated genes (in orange) as reported by Tine et al (2014). in the protein family encoding electroneutral cation-coupled chloride cotransporters that are important for many physiological processes that control cell volume, neuronal chloride concentration, intercellular ion movement and blood pressure (Arroyo et al, 2013).…”

Section: Selective Sweep Analysis In Cultivated European Sea Bassmentioning

confidence: 99%

Whole genome semiconductor based sequencing of farmed European sea bass (Dicentrarchus labrax) Mediterranean genetic stocks using a DNA pooling approach

et al. 2016

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European sea bass (Dicentrarchus labrax) is an important marine species for commercial and sport fisheries and aquaculture production. Recently, the European sea bass genome has been sequenced and assembled. This resource can open new opportunities to evaluate and monitor variability and identify variants that could contribute to the adaptation to farming conditions. In this work, two DNA pools constructed from cultivated European sea bass were sequenced using a next generation semiconductor sequencing approach based on Ion Proton sequencer. Using the first draft version of the D. labrax genome as reference, sequenced reads obtained a total of about 1.6 million of single nucleotide polymorphisms (SNPs), spread all over the chromosomes. Transition/transversion (Ti/Tv) was equal to 1.28, comparable to what was already reported in Salmon species. A pilot homozygosity analysis across the D. labrax genome using DNA pool sequence datasets indicated that this approach can identify chromosome regions with putative signatures of selection, including genes involved in ion transport and chloride channel functions, amino acid metabolism and circadian clock and related neurological systems. This is the first study that reported genome wide polymorphisms in a fish species obtained with the Ion Proton sequencer. Moreover, this study provided a methodological approach for selective sweep analysis in this species.

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“…Up to date, four WNK isoforms have been identified but only WNK2, WNK3, and WNK4 have been extensively studied (3). In regard to full-length WNK1 (L-WNK1), this kinase has been related to renal ion transport and neuronal chloride concentration (5,34,66).…”

Section: Spak; Wnk4; Xenopus Oocytes; Hek-293 Cells the Kmentioning

confidence: 99%

With no lysine L-WNK1 isoforms are negative regulators of the K⁺-Cl⁻ cotransporters

Mercado

Heros

Melo

et al. 2016

American Journal of Physiology-Cell Physiology

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ϩ -Cl Ϫ cotransporters (KCC1-KCC4) encompass a branch of the SLC12 family of electroneutral cation-coupled chloride cotransporters that translocate ions out of the cell to regulate various factors, including cell volume and intracellular chloride concentration, among others. L-WNK1 is an ubiquitously expressed kinase that is activated in response to osmotic stress and intracellular chloride depletion, and it is implicated in two distinct hereditary syndromes: the renal disease pseudohypoaldosteronism type II (PHAII) and the neurological disease hereditary sensory neuropathy 2 (HSN2). The effect of L-WNK1 on KCC activity is unknown. Using Xenopus laevis oocytes and HEK-293 cells, we show that the activation of KCCs by cell swelling was prevented by L-WNK1 coexpression. In contrast, the activity of the Na ϩ -K ϩ -2Cl Ϫ cotransporter NKCC1 was remarkably increased with L-WNK1 coexpression. The negative effect of L-WNK1 on the KCCs is kinase dependent. Elimination of the STE20 proline-alanine rich kinase (SPAK)/oxidative stress-responsive kinase (OSR1) binding site or the HQ motif required for the WNK-WNK interaction prevented the effect of L-WNK1 on KCCs, suggesting a required interaction between L-WNK1 molecules and SPAK. Together, our data support that NKCC1 and KCCs are coordinately regulated by L-WNK1 isoforms.

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The SLC12 family of electroneutral cation-coupled chloride cotransporters

Cited by 135 publications

References 68 publications

Physiological role of SLC12 family members in the kidney

Physiological role of SLC12 family members in the kidney

Whole genome semiconductor based sequencing of farmed European sea bass (Dicentrarchus labrax) Mediterranean genetic stocks using a DNA pooling approach

With no lysine L-WNK1 isoforms are negative regulators of the K⁺-Cl⁻ cotransporters

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The SLC12 family of electroneutral cation-coupled chloride cotransporters

Cited by 135 publications

References 68 publications

Physiological role of SLC12 family members in the kidney

Physiological role of SLC12 family members in the kidney

Whole genome semiconductor based sequencing of farmed European sea bass (Dicentrarchus labrax) Mediterranean genetic stocks using a DNA pooling approach

With no lysine L-WNK1 isoforms are negative regulators of the K+-Cl− cotransporters

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With no lysine L-WNK1 isoforms are negative regulators of the K⁺-Cl⁻ cotransporters