Disease relevance of SLC1A5

• A widely dispersed interference group of retroviruses that includes the feline endogenous virus (RD114), baboon endogenous virus (BaEV), human endogenous virus type W (HERV-W), and type D primate retroviruses uses the human Na(+)-dependent neutral amino acid transporter type 2 (hASCT2; gene name, SLC1A5) as a common cell surface receptor [1].
• Human endogenous retrovirus type W (HERV-W) envelope glycoprotein (Env) has recently been reported to induce fusion in cells expressing the RD-114 and type D retrovirus receptor (RDR) and to serve as a functional retroviral envelope protein [2].
• Spleen necrosis virus (SNV), a gammaretrovirus was chosen for testing resistance because it uses RDR to enter cells [2].
• In isolated perfused cotyledons, hypoxia also reduced syncytin (P<.05) but not ASCT2 messenger RNA [3].
• Expression of the glutamine transport protein ASCT2 in the human hepatoma cell line HepG2 is increased when cells are cultured in the presence of glutamine and this has been shown to be due to stimulation of the ASCT2 promoter [4].

Psychiatry related information on SLC1A5

• Exploratory regressions suggested that MDR/RDR students' math deficits or their underlying mechanisms explained a greater proportion of variance in responsiveness to problem-solving treatment than reading deficits or their underlying mechanisms [5].

High impact information on SLC1A5

• FN+ cells showed ruffled plasmalemma, dilated rough endoplasmic reticulin (RDR), and extracellular filamentous strands [6].
• To directly and more thoroughly investigate the receptor active sites, we constructed and analyzed a series of hASCT2/mASCT2 chimeras and site-directed mutants [1].
• N-linked glycosylation and sequence changes in a critical negative control region of the ASCT1 and ASCT2 neutral amino acid transporters determine their retroviral receptor functions [1].
• Consistent with their role as a battlefield in host-virus coevolution, the viral recognition regions in ASCT1 and ASCT2 of humans and mice are highly divergent compared with other regions of these proteins, and their ratios of nonsynonymous to synonymous nucleotide sequence changes are extremely large [7].
• Four intragenic polymorphic microsatellite markers, AAAT Alu repeat, IVS27AC28.4, ACI27.2, and IVS38GT53.0, located along a 65 kb DNA region of the NF1 gene, were used to genotype 64 Spanish families with neurofibromatosis type 1 (NF1) [8].

Chemical compound and disease context of SLC1A5

• RESULTS: Hypoxia, deferoxamine, and cobalt chloride markedly decreased syncytin messenger RNA in BeWo cells, whereas ASCT2 messenger RNA was not altered significantly [3].
• The pH-dependent functional activation of ASCT2 and the ASCT2-mediated glutamate uptake may play important roles during ischemic acidosis or synaptic activity-induced local acidification [9].
• We extended these observations to other forms of experimental inflammation, including streptococcal cell wall polysaccharide- and adjuvant-induced arthritides and peptide R16 (epitope of the interphotoreceptor retinoid-binding protein)-induced uveitis in Lewis rats [10].

Biological context of SLC1A5

• However, SLC1A5 was not linked to the Hartnup phenotype in other families [11].
• These mutations did not alter the predicted amino acid sequence of SLC1A5 and were considered unlikely to play a role in Hartnup disorder [11].
• These results suggested that functional up-regulation of ASCT2 by SNAP might be partially associated with an increase in the density of transporter protein via de novo synthesis [12].
• OBJECTIVE: The purpose of this study was to test the hypothesis that hypoxia down-regulates placental syncytin, which could play a role in altered placentogenesis; we investigated the influence of hypoxia on syncytin and its receptor ASCT2 gene expression in BeWo cells and in ex vivo perfused human cotyledons [3].
• The gene encoding a human neutral amino acid transporter-like protein (SLC1A5) was mapped to chromosome band 19q13.3 by fluorescence in situ hybridization to metaphase chromosomes [13].

Anatomical context of SLC1A5

• We describe the regulation mechanisms of the Na(+)-dependent neutral amino acid transporter ASCT2 via nitric oxide (NO) in the human intestinal cell line, Caco-2 [12].
• Functional regulation of Na+-dependent neutral amino acid transporter ASCT2 by S-nitrosothiols and nitric oxide in Caco-2 cells [12].
• Transcriptional effects of hypoxia on fusiogenic syncytin and its receptor ASCT2 in human cytotrophoblast BeWo cells and in ex vivo perfused placental cotyledons [3].
• C6 cells cultured both in the presence and absence of Gln expressed ASCT2 mRNA, indicating that system ASCT2-mediated Gln uptake is modulated at a posttranscriptional level [14].
• In contrast, the profile for rat astrocytes was a mixture of that for HEK293 cells expressing rat ASCT1 and that for the cells expressing rat ASCT2 [15].

Associations of SLC1A5 with chemical compounds

• Identification of the hASCT2-binding domain of the Env ERVWE1/syncytin-1 fusogenic glycoprotein [16].
• Identification of the promoter elements involved in the stimulation of ASCT2 expression by glutamine availability in HepG2 cells and the probable involvement of FXR/RXR dimers [4].
• Exclusion of linkage between schizophrenia and the gene encoding a neutral amino acid glutamate/aspartate transporter, SLC1A5 [17].
• Photolytic release of free alanine results in the generation of significant transient current components in HEK293 cells expressing the ASCT2, SNAT1, and SNAT2 proteins [18].
• RESULTS: Hematologic recovery was normal after ASCT1 but delayed platelet recovery was observed after ASCT2 with busulfan in the conditioning regimen [19].

Physical interactions of SLC1A5

• These results show that the stimulation of ASCT2 expression in response to glutamine in part involves binding of FXR/RXR to the ASCT2 promoter [4].

Regulatory relationships of SLC1A5

• Expression of the ASCT2 transporter in HepG2 hepatoma cells is stimulated by glutamine by a pathway involving the promoter element AGGTGAATGACTT which binds FXR/RXR dimers [20].
• High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes [9].

Other interactions of SLC1A5

• RT-PCR revealed that Caco-2 cells expressed the Na(+)-dependent neutral amino acid transporter ASCT2, but not the other Na(+)-dependent neutral amino acid transporters ATB(0,+) and B(0)AT1 [12].
• To elucidate whether SLC1A5 is involved in the aetiology of cystinuria, we screened two non-type I cystinuria families without detectable mutations inSLC7A9 (and SLC3A1) but compatible with linkage to 19q13 for genomic variants in SLC1A5 [21].
• Here, we describe a new photolabile alanine derivative based on protection of alanine with the 4-methoxy-7-nitroindolinyl (MNI) caging group, which we use for pre-steady-state kinetic analysis of alanine transport by ASCT2, SNAT1, and SNAT2 [18].
• METHODS: The quantitative real-time polymerase chain reaction was used to study the syncytin and ASCT2 expression during placental development in 35 placentas from women without pre-eclampsia (ranged from 5 to 40 weeks of gestation) and the alterations of pre-eclamptic placentas (n=16) compared with gestational-age-matched controls (n=16) [22].
• According to kinetic analysis and chemiluminescence assays, SGK1 and SGK3 modulate hASCT2 by enhancing the transporter abundance in the plasma membrane [23].

Analytical, diagnostic and therapeutic context of SLC1A5

• Quantitative RT-PCR of SLC1A5 messenger RNA in affected and unaffected subjects did not support systemic differences in expression as an explanation for Hartnup disorder [11].
• By deletion and site-directed mutagenesis, cell-free translation, and analyses of epitope-tagged ASCT2 proteins synthesized intracellularly, we determined that the truncated mRNA encodes multiple ASCT2 isoforms with distinct amino termini that are translationally initiated by a leaky scanning mechanism at these CUG and GUG codons [24].
• ASCT1 was conditioned with CBV + mitoxantrone (30 mg/m2) and ASCT2 (cytarabine 6 g/m2 melphalan 140 mg/m2 and total body irradiation at 12 Gy or busulfan 16 (n = 4) than 12 mg/kg) [19].
• Immunoblotting detected ASCT2 in neural retina and in 1 degrees MCs; immunohistochemistry confirmed these data in retinal sections and in cultures of 1 degrees MCs [25].
• RDR is defined as the percentage increase in plasma retinol level relative to the plasma retinol level 5 h after the oral administration of a standard oral dose (450 micrograms) of retinyl acetate [26].

References