Disease relevance of Slc13a1

• Sulfate homeostasis, NaSi-1 cotransporter, and SAT-1 exchanger expression in chronic renal failure in rats [1].
• Two mammalian sodium-dependent anion-cotransporters (NaPi-2 for phosphate and NaSi-1 for sulfate) have been expressed in Sf9 insect cells using the baculovirus expression system [2].
• The purpose of the present study was to determine the effect of metabolic acidosis (MA) on Na-Si cotransport activity and NaSi-1 protein and mRNA expression [3].
• These results demonstrate that PTU-induced hypothyroidism decreases sodium-sulfate cotransport by downregulation of the NaSi-1 gene [4].

High impact information on Slc13a1

• NaSi-1 cRNA leads in a time- and dose-dependent manner to specific stimulation of Na(+)-dependent SO4(2-) uptake in oocytes [5].
• The apparent affinity constants of the NaSi-1 cRNA-expressed transport resemble those of Na+/SO4(2-) cotransport in brush-border membrane [5].
• In vitro translation of NaSi-1 cRNA results in a protein of the expected size and suggests glycosylation [5].
• NaDC-1 protein contains eight putative transmembrane domains, and the sequence and secondary structure are related to the renal Na+/sulfate transporter, NaSi-1 [6].
• The Na+/sulfate cotransporter cloned from rat kidney cortex (NaSi-1) has been expressed in oocytes of Xenopus laevis and subjected to electrophysiological analysis by current and voltage clamp methods [7].

Biological context of Slc13a1

• It differs to the renal NaSi-1 only in the length of the 3' untranslated region, suggesting that the major difference lies in the differential use of polyadenylation signals [8].
• Ileal NaSi-1 cDNA contains 2722 base pairs (bp), almost 500 bp more than the renal NaSi-1 cDNA; however, it encodes a protein of 595 amino acids identical to the renal NaSi-1 protein [8].
• Therefore, MPL treatment increases the renal clearance of inorganic sulfate, at least in part, due to down-regulation of NaSi-1 mRNA and protein expression in the kidney [9].
• Sulfate homeostasis by renal reabsorption is maintained by an up-regulation of steady state levels of NaSi-1 mRNA and protein when the diet is low in methionine [10].
• A Na+/SO4(2-)-cotransport system was recently identified from a rat kidney cortex cDNA library by expression cloning (NaSi-1;) [11].

Anatomical context of Slc13a1

• Northern blot analysis shows strong signals in rat lower small intestine and kidney cortex (2.9 x 10(3) and 2.3 x 10(3) bases), with the ileal NaSi-1 corresponding to the longer transcript [8].
• For NaSi-1 protein expression, translational or posttranslational mechanisms may maintain equal numbers of sulfate proteins on proximal tubular membranes during maturation, whereas sat-1 protein levels are in close agreement with mRNA changes [12].

Associations of Slc13a1 with chemical compounds

• Electrogenic cotransport of Na+ and sulfate in Xenopus oocytes expressing the cloned Na+SO4(2-) transport protein NaSi-1 [7].
• 35S-sulfate uptake was determined in Madin-Darby canine kidney (MDCK)/NaSi-1 cells (MDCK cells that have been stably transfected with rat sodium/sulfate co-transporter (NaSi-1) cDNA) and in opossum kidney (OK) cells [13].
• Increased mRNA and protein levels for the sodium/sulfate transporter (NaSi-1) were found in the kidney cortex following treatment with the 0 and 0.3% methionine diet groups [10].
• Functional expression and purification of histidine-tagged rat renal Na/Phosphate (NaPi-2) and Na/Sulfate (NaSi-1) cotransporters [2].
• In the present work expression along the nephron of the Na/SO4-cotransporter NaSi-1 was studied by immunofluorescence [14].

Other interactions of Slc13a1

• Using a rat renal Na(+)-sulphate cotransporter cDNA as a probe [NaSi-1; Markovich et al. (1993) Proc Natl Acad Sci USA 90:8073-8077], the highest hybridization signals (2.3 kb and 2.9 kb) were obtained in size fractions showing the highest expression of Na(+)-dependent sulphate transport in oocytes [15].
• Recently, we cloned a cDNA (NaSi-1) localized to rat renal proximal tubules and encoding the brush-border membrane (BBM) Na gradient-dependent inorganic sulfate (Si) transport protein (Na-Si cotransporter) [3].
• Sodium-dependent sulfate transporter (NaSi-1) mRNA and protein levels were significantly lower in the kidney cortex from hypothyroid rats [4].
• At early stages of cyst development, alkaline phosphatase, aquaporin-1, NaSi-1 cotransporter, and Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) were expressed normally [16].

Analytical, diagnostic and therapeutic context of Slc13a1

• The 43% decrease in BBM Na/Si cotransport activity was associated with a 33% decrease in BBM NaSi-1 protein abundance, as determined by Western blotting, and a 2.7-fold decrease in cortical NaSi-1 mRNA abundance, as determined by Northern blotting [17].
• NaSi-1 mRNA was determined by RT-PCR and protein levels by ELISA [13].
• Kidney cortex sodium/sulfate cotransporter (NaSi-1) mRNA levels were determined by reverse transcription-polymerase chain reaction and NaSi-1 protein levels were determined by enzyme-linked immunosorbent assay [9].
• The Vmax for the sodium-dependent sulfate cotransport (NaSi-1) in BBM was significantly lower in the IBU group compared with the control group (0.79 +/- 0.23 vs. 1.25 +/- 0.17 nmol/mg protein/10 sec, respectively; P <.05) with no change in Km [18].

References