Disease relevance of SLC13A1

• Both NaSi-1 and Sat-1 transporter activities are implicated in pathophysiological states such as heavy metal intoxication and chronic renal failure [1].
• A syndrome of congenital hypoplasia of the alae nasi, situs inversus, and severe hypoproteinemia in two siblings [2].
• 3. In six additional normal subjects and three subjects with obstructive sleep apnoea, we studied the alae nasi EMG activity during steady-state hypercapnia with PCO2 held constant 5 torr (0.7 kPa) above baseline [3].
• The main features were severe hypertelorism, downward slanted palpebral fissures, bilateral epicanthal folds, a grossly deformed nose with notched alae nasi, absent nasal tip and long philtrum [4].
• As the duration of each apnea increased, the activation of alae nasi EMG occurred progressively earlier than the change in esophageal pressure [5].

Psychiatry related information on SLC13A1

• An infant with aplastic alae nasi, imperforate anus, focal aplasia cutis over the fontanels, microcephaly, and mental retardation is presented as an example of the Johanson-Blizzard syndrome [6].
• There were no significant differences in minute ventilation, tidal volume, or any index of genioglossus or alae nasi EMG amplitude between non-REM (NREM) and REM sleep, when REM was analyzed as a single sleep stage [7].
• Because certain pharmacologic agents differentially influence upper airway and diaphragm motor activity, we postulated that the adenosine antagonist theophylline might preferentially increase alae nasi activity in human subjects [8].
• Electromyographic recordings of the genioglossus and alae nasi muscles with and without NAPP during wakefulness in five of the OSA and five of the normal subjects showed either a decrease or no change in phasic and tonic activity with NAPP [9].

High impact information on SLC13A1

• In the present study, we identified two loss-of-function polymorphisms in the human NaS1 gene and showed the Nas1-null mouse to be hypersensitive to APAP hepatotoxicity [10].
• APAP treatment led to increased liver damage and decreased hepatic glutathione levels in the hyposulfatemic Nas1-null mice compared with that in normosulfatemic wild-type mice [10].
• Previous reports have shown that the hyperpolarizing response to light and the light-activated outward current are mediated by an increase of a conductance of K+ channels in the plasma membrane (Gorman and McReynolds, 1974; Gomez and Nasi, 1994a) [11].
• The low affinity Na+/sulfate cotransporter, NaSi-1, belongs to the SLC13 family that also includes the Na+/dicarboxylate cotransporters, NaDC [12].
• Serines 260 and 288 are involved in sulfate transport by hNaSi-1 [12].

Chemical compound and disease context of SLC13A1

• To investigate this hypothesis we studied the effect of alpha-methyldopa on alae nasi electromyographic (EMG) activity during hypercapnia [3].
• A case of lymphocutaneous sporotrichosis that had developed from the dorsum nasi to the left buccal region of a 65-year-old woman was treated with itraconazole 100 mg day-1 [13].
• This disorder is identical with the "syndrome of congenital aplasia of the alae nasi, deafness, hypothyroidism, dwarfism, absent permanent teeth and malabsorption" subsequently reported by Johanson and Blizzard [14].

Biological context of SLC13A1

• Knowledge of the structure, function, and chromosomal localization of hNaSi-1 will permit the screening of NAS1 mutations in humans with disorders in renal sulfate reabsorption and homeostasis [15].
• The NAS1 gene contains 15 exons, spanning over 83 kb in length [15].
• Mutagenesis of the N-glycosylation site of hNaSi-1 reduces transport activity [16].
• The amino acid sequence of hNaDC-1 is 78% identical to the rabbit renal Na(+)-dicarboxylate cotransporter, NaDC-1, and 42% identical to the rat renal Na(+)-sulfate transporter, NaSi-1 [17].
• Contrary to NaSi-1, no physiological factor has been found to date to regulate Sat-1 gene expression [1].

Anatomical context of SLC13A1

• Wild-type hNaSi-1 and two N-glycosylation site mutant proteins, N591Y and N591A, were functionally expressed and studied in Xenopus oocytes [16].
• The antibodies recognized native NaSi-1 proteins in pig and rat brush-border membrane vesicles as well as the recombinant proteins expressed in Xenopus oocytes [16].
• Recently, NaSi-1 was shown to be regulated at the protein and mRNA level by a number of factors, such as vitamin D, dietary sulfate, glucocorticoids and thyroid hormones, which are known to modulate sulfate reabsorption in vivo [1].
• The scalp, forehead, external auditory canal, alae nasi, anterior nares, groin, rectum, and antecubital and popliteal fossa were sampled [18].
• Two SO(4)2- transporters that have been characterized and implicated in regulating serum SO4(2-) levels are: NaSi-1, a Na+-SO(4)2- cotransporter located at the brush border membrane and Sat-1, a SO4(2-)-anion exchanger located on the basolateral membranes of proximal tubular cells [19].

Associations of SLC13A1 with chemical compounds

• Alanine substitution of Ser-260 resulted in increased Km values for both substrate and Na+ whereas alanine replacement at Ser-288 resulted in a broadened cation selectivity, indicating that these two serines might play important roles in cation and/or substrate binding of hNaSi-1 [12].
• Two serine residues in hNaSi-1, at positions 260 and 288, are conserved in all of the sulfate transporters in the family whereas the NaDC contain alanine or threonine at those positions [12].
• Although the cell surface abundance of the two glycosylation site mutants, N591Y and N591A, was greater than that of wild-type hNaSi-1, both mutants had greatly reduced Vmax, with no change in Km [16].
• Expression of hNaSi-1 protein in Xenopus oocytes demonstrated a high-affinity Na+-sulfate cotransporter that was inhibited by selenate, thiosulfate, molybdate, tungstate, citrate, and succinate [15].
• Analysis of urinary APAP metabolites revealed a significantly lower ratio of APAP-sulfate to APAP-glucuronide in the Nas1-null mice [10].

Other interactions of SLC13A1

• To study this further, NaSi-1 (SLC13A1) and Sat-1 (SLC26A1) gene structures were determined and recent studies have characterized their respective gene promoters [19].

Analytical, diagnostic and therapeutic context of SLC13A1

• Polyclonal antibodies against a glutathione S-transferase fusion protein containing a 65-amino acid peptide of hNaSi-1 (GST-Si65) were raised in rabbits, purified, and then used in Western blotting and immunofluorescence experiments [16].
• The facies are characterised by square configuration, tented upper lip, and thickening of the helices, upper eyelids, and alae nasi [20].
• Alae nasi EMG was recorded in 10 normal men under the following conditions: 1) nasal breathing (all potential nasal receptors exposed), 2) oral breathing (nasal receptors not exposed), 3) nasal breathing with splints (airway deformation prevented), and 4) nasal breathing after nasal anesthesia (mucosal receptors anesthetized) [21].
• During each trial we recorded EMG signals from the alae nasi and diaphragm before and after intravenous infusion of either aminophylline or placebo [8].
• He had a long broad nose with hypoplasia of the alae nasi, conductive hearing loss requiring hearing aids, muscular build, stiff spine, prominent acromia, pectus excavatum, ischial prominences, short fifth fingers, fusion at the proximal interphalangeal joints of the fifth fingers with indistinct overlying creases, and toe syndactyly [22].

References