Solute Carrier Family 12 (Sodium/potassium/chloride Transporters), Member 1 Proteine (SLC12A1)

Human Solute Carrier Family 12 (Sodium/potassium/chloride Transporters), Member 1 (SLC12A1) Interaktionspartner

1. We replicated the methods in a previous study to detect rare and potentially loss-of-function variants in SLC12A3, SLC12A1, and KCNJ1 reducing blood pressure in variant carriers as compared with noncarriers using whole exome sequencing data. Our study confirmed that SLC12A3, SLC12A1, and KCNJ1 are indeed genes protective of hypertension in the general population.

2. an association between primary hyperparathyroidism and loss of function mutation of SLC12A1, which may result in an aberrant threshold of the calcium sensing receptor at the level of the kidney, is reported.

3. A novel variant in the SLC12A1 gene, c.1614T>A, which predicts a change from a tyrosine codon to a stop codon (p.Tyr538Ter) was found in two families with Bartter syndrome type I.

4. Low SLC12A1 urine levels were associated with Bartter syndrome.

5. Mutations in SLC12A1 gene is associated with Bartter syndrome.

6. Urinary NKCC2 increased in chronic kidney disease patients and decreased in controls in response to hypertonic saline.

7. The association between polymorphisms in KCNJ1, SLC12A1, and 7 other genes and calcium intake and colorectal neoplasia risk was studied.

8. overexpression of mammalian plasma-membrane Na+-K+-2Cl- co-transporter NKCC2 in yeast cells complements the phenotypes resulting from the deletion of the VHC1 gene.

9. Review summarizes three human disorders that have been linked to the mutation/dysfunction of Na-Cl, Na-K-2Cl, and K-Cl cotransporters (Bartter's, Gitleman's, and Andermann's syndromes).

10. NKCC2 mutations result in impaired apical targeting and function of NKCC2 transporter and give rise to a pathological phenotype known as type I Bartter syndrome. (Review)

11. Data show that intracellular association between WNK1 and oxidative stress-responsive 1 (OSR1) is required for stimulation of OSR1 and Na(+), K(+), Cl(-)-Cotransporter NKCC1 and NKCC2 activities by osmotic stress.

12. NKCC1 and NKCC2 were expressed in the gastric mucosa of rat, mouse and human.

13. The Wnk3 protein isoforms have a similar effect on SLC12 cotransporters. NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions.

14. two mutations in the SLC12A1 among patients suffering from bartter and Gitelman syndromes

15. NKCC2 is expressed widely in the colonic epithelium in thecolon, especially in the apical membrane. It involves the process of colonic Cl(-) absorption coupled with HCO(3)(-) secretion.

16. Data demonstrate that hypotonic low-chloride conditions that activate the WNK1-SPAK and OSR1 pathway promote phosphorylation of NKCC2 isoforms.

17. Investigated functional consequences of nine rare independed mutations in NKCC2 gene. defects in NKCC2 processing, transport turnover rate, regulation, and ion affinity contribute to impaired transport function in six of the nine identified mutants.

18. In schizophrenia, increased expression levels of OXSR1 and WNK3 may shift the balance of chloride transport by NKCC1 and KCC2 and alter the nature of gamma-aminobutyric acid neurotransmission in the prefrontal cortex.

19. SLC12A1 mutations are associated with Bartter syndrome.

20. he human NKCC2 is an example of how differential splicing forms the basis for a diversification of transporter protein function

Cow (Bovine) Solute Carrier Family 12 (Sodium/potassium/chloride Transporters), Member 1 (SLC12A1) Interaktionspartner

1. SLC12A1 (g.62382825G>A, p.Pro372Leu) is a hypomorphic or loss-of-function mutation and the hydrallantois with this mutation shows incomplete penetrance in Japanese Black cattle.

Mouse (Murine) Solute Carrier Family 12 (Sodium/potassium/chloride Transporters), Member 1 (SLC12A1) Interaktionspartner

1. The differential regulation of ROMK, large-conductance Ca(2+)-activated K(+) (BK) channel, BK-alpha and NKCC2 between female and male mice, at least, were partly mediated via WNK1 pathway, which may contribute to the sexual dimorphism of plasma K(+) and blood pressure control.

2. VAMP3 is required for normal NKCC2 expression, renal function, and blood pressure.

3. IL-1 receptor (IL-1R1) deficiency or blockade limits blood pressure elevation in this model by mitigating sodium reabsorption via the NKCC2 co-transporter in the nephron.

4. Data suggest renal cell lines exhibit an OS9- (osteosarcoma amplified 9 protein-)mediated ERAD (endoplasmic reticulum-associated degradation) pathway that degrades Nkcc2/Slc12a1 prior to glycosylation/processing.

5. The findings demonstrated a substantial role of mitochondrial dysfunction in mediating the downregulation of NKCC2 and ENaCalpha in obstructive kidney disease, possibly via iNOS-derived nitric oxide and BNP.

6. our results suggest that NKCCs are involved in insulin secretion and that a single Slc12a2 allele may protect beta-cells from failure due to increased homeostatic expression of Slc12a1.

7. Vasopressin plays an important role in the colonic epithelia by stimulating NKCC2 trafficking to the apical membrane and inducing NKCC2-mediated ion transport.

8. In this systemic analysis no clear primary effects of the Slc12a1I299F mutation appeared for the organs other than the kidneys where Slc12a1 expression has been described.

9. increased phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter in obesity and identifies a new role for AMP-activated protein kinase in regulating the activity of oxidative stress responsive 1 kinase-related proline-alanine-rich protein kinase

10. Differential splicing of NKCC2 contributes to the adaptive capacity of the kidney to cope with changes in reabsorptive needs.

11. NKCC2A-dependent activation of NFAT5 is part of a pathway by which the medullary thick ascending limb produces TNF in response to hypertonic NaCl intake.

12. Abnormal anterograde trafficking as a common mechanism associated with mutations depriving NKCC2.

13. NKCC1 and NKCC2 were expressed in the gastric mucosa of rat, mouse and human.

14. In the kidneys, NKCC2 but not NCC is the main target of OSR1 and the reduced p-NKCC2 in KSP-OSR1(-/-) mice may lead to a Bartter-like syndrome.

15. a permissive role for THP in the modulation of NKCC2-dependent TAL salt reabsorptive function.

16. these findings suggest that TNF plays a role as an endogenous inhibitor of NKCC2 expression and function

17. These findings suggest that NKCC2A and NKCC2F exhibit differential effects on NFAT5 expression and transcriptional activity in response to hypertonicity produced by high NaCl concentration.

18. WNK1 is a negative regulator of NCC and NKCC2 in vivo and plays an important role in the control of Na(+) homeostasis and blood pressure.

19. SCAMP2 regulates NKCC2 transit through recycling endosomes and limits the cell surface targeting of the co-transporter by interfering with its exocytotic trafficking.

20. These data suggest a novel regulatory pathway whereby intracellular trafficking of SPAK by the sorting receptor SORLA is crucial for proper NKCC2 activation and for maintenance of renal ion balance.