Disease relevance of SLC38A1

• We demonstrate major power advantages of our method both in analysis of data from a case-control study of the association between colorectal adenoma and DNA variants in the NAT2 genomic region, which are well known to be related to a common biological phenotype, and under different models of gene-gene interactions with use of simulated data [1].
• Characterization of In3Mor, a new integron carrying VIM-1 metallo-{beta}-lactamase and sat1 gene, from Morganella morganii [2].
• Hypoxia decreased expression of hATA1 and hATA2 in both trophoblast phenotypes [3].
• To clarify the potential modifying role of the NAT2 acetylator status in microsatellite stable (MSS) colorectal cancer (CRC), we studied 140 patients with sporadic CRC (group 1) and 69 patients with CRC who met at least one criterion of the revised Bethesda guidelines (group 2) [4].

Psychiatry related information on SLC38A1

• Allelic variants of the NAT2 gene are determined by a pattern of single nucleotide polymorphisms (SNPs) resulting in slow (SA), intermediate (IA) or rapid acetylator (RA) phenotypes and causing the individual differences in the NAT2 metabolic capacity [4].

High impact information on SLC38A1

• Recently, we cloned the ATA/SNAT transporters responsible for amino acid transport system A. System A is one of the major transport systems for small neutral and glucogenic amino acids represented by alanine and is involved in the metabolism of glucose and fat [5].
• Glycine (GLYT1) and small neutral amino-acid (SNAT) transporters, which regulate glycine levels, represent additional targets for drug development, and may represent a site of action of clozapine [6].
• Photolytic release of free alanine results in the generation of significant transient current components in HEK293 cells expressing the ASCT2, SNAT1, and SNAT2 proteins [7].
• Our findings support a role for glutamine transport through SNAT1 and/or SNAT2 in the maintenance of abnormal activity in this in vitro model of epileptogenesis and suggest that system A transport and glutamine metabolism are potential targets for pharmacological intervention in seizures and epilepsy [8].
• We show that slices from injured cortex take up glutamine more readily than control slices, and an increased expression of the system A transporters SNAT1 and SNAT2 likely underlies this difference [8].

Biological context of SLC38A1

• This report describes the primary structure and functional characteristics of human ATA1, a subtype of the amino acid transport system A. The human ATA1 cDNA was isolated from a placental cDNA library [9].
• Downregulated genes in the signature were the glutamine transporter SLC38A1, a TRAF-6 inhibitory zinc finger protein, and membrane-bound transcription factor protease S2P, among others [10].
• For SNAT1, these transient currents differ in their time course (tau = 1.6 ms) from previously described pre-steady-state currents generated by applying steps in the membrane potential (tau approximately 4-5 ms), indicating that they are associated with a fast, previously undetected, electrogenic partial reaction in the SNAT1 transport cycle [7].
• There were no differences in SNAT1 and SNAT2 mRNA expression with gestation [11].
• The SAT1 flipping method relies on the use of a cassette that contains a dominant nourseothricin resistance marker (caSAT1) for the selection of integrative transformants and a C. albicans-adapted FLP gene that allows the subsequent excision of the cassette, which is flanked by FLP target sequences, from the genome [12].

Anatomical context of SLC38A1

• To rule out a possible influence of fixation and procedural variables on detection of SNAT1 and SNAT2 immunoreactivity in axon terminals, we used non-conventional immunocytochemical methods, which, in certain cases, improve antigen detection [13].
• The activation of SNAT may be due to a stimulation of the sympathetic nervous system (urinary noradrenaline; NA: +243%, p < 0.005) when the cellular immune system responded towards tumor growth (urinary biopterin, +214%, p < 0.005) [14].
• However, the results of our confocal and electron microscopy immunocytochemical studies of the localization of these transporters in the cerebral cortex show that SNAT1 and SNAT2 are robustly expressed in the somatodendritic domain of cortical neurons, but rarely to axon terminals [13].
• The expression of ASCT2 mRNA (system ASC), ATA1 mRNA (system A) and SN2(SNAT5) mRNA (system N) were not affected by AI in either of the cell lines [15].
• Transport proteins are also present within marginal giant cells and, for SNAT1, within fetal endothelium [16].

Associations of SLC38A1 with chemical compounds

• Results The strain contained In3Mor, a novel class 1 integron carrying a carbapenemase gene (bla(VIM-1)) associated with a trimethoprim (dfrA1), a streptothricin (sat1) and two aminoglycoside resistance genes (aacA7 and aadA1) [2].
• At passage 12 SNAT and N-acetylserotonin were unaffected but a depletion of plasma tryptophan (-34%, p < 0.0001), the precursor amino acid of melatonin, was found [14].
• Our data thus suggest that neither SNAT1 nor SNAT2 meet the criteria for their postulated role in the "glutamate-glutamine" cycle, and indicate that other Gln transporters (either orphan or yet to be identified) must be expressed at axon terminals and sustain the Glu (and gamma-aminobutyric acid) neurotransmitter pool (s) [13].

Analytical, diagnostic and therapeutic context of SLC38A1

• Immunohistochemistry demonstrates the presence of SNAT1 and 2 within the placental labyrinth at both days 14 and 20 [16].
• Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) we quantified the mRNA for two system A subtype target genes ATA1 and ATA2 as well as beta-actin for normalization [17].
• Those mAbs could be used for sandwich radioimmunoassay of HuIFN-gamma using double mAbs in two combinations, one (G4-15/E4-18) based on dimer forms of HuIFN-gamma and the other (SAT-1/E4-18) based on epitope difference [18].
• The methodology is implemented in an original meta-analysis of studies relating the risk of bladder cancer to two N-acetyltransferase genes, NAT1 and NAT2, and smoking status [19].
• Transporter (sodium coupled neutral amino acid transporter (SNAT1/2)) expression was analysed at mRNA and protein level by Northern and Western blotting respectively [20].

References