High impact information on SLC7A8

• We have identified two new transcripts (SLC7A8 and SLC7A7) homologous to amino acid transporters, highly expressed in kidney and mapping in the LPI critical region [1].
• CD98/LAT-2 interacts with ICAM-1 in Caco2-BBE cell monolayers, and (ii) [2].
• CD98 was found to selectively coimmunoprecipitate with both LAT-2 and beta(1) integrin, and, logically, all three proteins were polarized to the same (basolateral) domain [3].
• Basolateral LAT-2 has a major role in the transepithelial flux of L-cystine in the renal proximal tubule cell line OK [4].
• This study shows the expression of system L and y(+)L transport activities in the basolateral domain of the proximal tubule-derived cell line OK and the cloning of the corresponding LAT-2 and y(+)LAT-1 cDNAs [4].

Biological context of SLC7A8

• RNA in situ hybridization data on mouse embryos confirm the expression in kidney and intestine and, interestingly, reveal that SLC7A8 is also highly expressed in eye, in retinal pigmented epithelium, and in tooth buds at day 16.5 of gestation [5].
• Stable transfection with a LAT-2 antisense sequence demonstrated the specific role of LAT-2 in the basolateral system L amino acid exchange activity in OK cells [4].
• Cloning and gene silencing of LAT2, the L-3,4-dihydroxyphenylalanine (L-DOPA) transporter, in pig renal LLC-PK1 epithelial cells [6].
• Organ-specific overexpression of type 2 L-amino acid transporter (LAT2) in the kidney of the spontaneous hypertensive rat (SHR), accompanied by an enhanced ability to take up L-DOPA, may constitute the basis for the enhanced renal production of dopamine in the SHR in an attempt overcome the deficient dopamine-mediated natriuresis [6].

Anatomical context of SLC7A8

• The affinity and the inhibition profiles of [14C]L-leucine uptake by various amino acids in the FOB and Saos2 cells were comparable with those for the LAT2 and LAT1 expressed in Xenopus oocytes, respectively [7].

Associations of SLC7A8 with chemical compounds

• SLC7A8, a gene mapping within the lysinuric protein intolerance critical region, encodes a new member of the glycoprotein-associated amino acid transporter family [5].
• The homology data and the expression pattern are in agreement with the hypothesis that SLC7A8 represents a novel light chain interacting with the 4F2 heavy chain in the multimeric complex mediating neutral and/or cationic amino acid transport and cystine/glutamate exchange [5].
• This demonstrates that LAT-2 plays a major specific role in the net basolateral efflux of cysteine and points to LAT-2 as a candidate gene to modulate cystine reabsorption [4].
• In contrast, the content of serine, threonine, and alanine showed a tendency to decrease, whereas other LAT-2 substrates were not affected [4].
• No significant correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2 with melphalan pharmacokinetics or with melphalan side effects [8].

Regulatory relationships of SLC7A8

• CD98 and ICAM-1 ligands generate intracellular signals that regulate the amino acids transporter (LAT-2) activity [2].

Other interactions of SLC7A8

• ICAM-1 was found to be expressed to the basolateral domain and to selectively coimmunoprecipitate with CD98/LAT-2 in Caco2-BBE monolayers [2].
• System L type amino acid transporter 2 (LAT2) expression was not changed by amino acid restriction, indicating that the responses seen in the system A transporters were not a general cell response [9].

Analytical, diagnostic and therapeutic context of SLC7A8

• Levels of LAT2 cDNA, determined by real-time quantitative RT-PCR, were markedly (P<0.05) reduced by LAT2 siRNA but not by the mismatch LAT2 siRNA [6].

References