Disease relevance of SLC7A1

• In both Xenopus laevis oocytes and U373MG glioblastoma cells, PMA treatment promoted the internalization of hCAT-1 (fused to the enhanced green fluorescence protein (EGFP)) as visualized by fluorescence microscopy [1].
• Reduction of the ornithine transport via CAT-1 may be a new target for treatment of gyrate atrophy [2].
• Hepatocytes carrying the murine cytomegalovirus immediate early promoter (pUCRNmCMVX/HCAT) also had appreciable CAT activity [3].
• Antithyroid treatment (carbimazole and propranolol) was instituted, and his diarrhea subsided with the control of hyperthyroidism (free thyroxine, 15 pmol/L) along with an improvement of bile acid absorption (Se-HCAT retention, 14.7%) [4].

High impact information on SLC7A1

• The derepression requires binding of HuR, an AU-rich-element binding protein, to the 3'UTR of CAT-1 mRNA [5].
• The derepression of CAT-1 mRNA is accompanied by its release from cytoplasmic processing bodies and its recruitment to polysomes [5].
• The human cationic amino acid transporter hCAT-1 is almost ubiquitously expressed and probably the most important entity for supplying cells with extracellular arginine, lysine, and ornithine [1].
• PKC did not phosphorylate hCAT-1 directly as evidenced by in vivo phosphorylation experiments and mutational analysis, indicating an indirect action of PKC on hCAT-1 [1].
• Alanine scanning mutagenesis of highly conserved residues within HCAT identified one mutation (D893A) that destroyed enzyme activity but not the ability of the mutant subunit to form homodimers [6].

Biological context of SLC7A1

• Southern blot analysis of genomic DNA from a panel of 48 mouse-human somatic cell hybrids assigned the human version of this gene, ATRC1, to chromosome 13 [7].
• Expression of the putative cyclase catalytic region (HCAT) resulted in the formation of an active enzyme that migrated as a homodimer on gel filtration columns; treatment with sodium trichloroacetate caused dissociation of the dimer and a loss of cyclase activity [6].
• Chloramphenicol (cat1), kanamycin (aph), sulfonamide (sul2), and tetracycline (tetG) resistance genes were also carried on the plasmid within the same 19-kb region [8].

Anatomical context of SLC7A1

• System y+ plays a minor role in arginine uptake by monocytes and the expression of system y+-related genes, SLC7A1 and SLC7A2, is not changed by IFNgamma [9].
• We report here that the system y+ cationic amino acid transporter ATRC1 localized to clusters within the basolateral membrane of polarized Madin-Darby canine kidney and human embryonic kidney (HEK) cells, suggesting that the transporters are restricted to discrete membrane microdomains in epithelial cells [10].
• In agreement with these findings, cytochalasin D reduced the amount of ATRC1 associated with the actin membrane cytoskeleton [10].
• Based on solubility in nonionic detergents, two populations of ATRC1 molecules existed: approximately half of the total ATRC1 in HEK cells associated with the actin membrane cytoskeleton, whereas another one-fourth resided in detergent-resistant membranes (DRM) [10].
• Although some ATRC1 clusters in HEK cells colocalized with caveolin, the majority of ATRC1 did not colocalize with this marker protein for a type of DRM called caveolae [10].

Associations of SLC7A1 with chemical compounds

• Further, CAT-1 silencing by siRNA reduced ornithine cytotoxicity in OAT-deficient RPE cells [2].
• Using reverse transcription-polymerase chain reaction (RT-PCR), Northern blotting, and immunohistochemistry, we found a significant increase in glomerular cationic amino acid transporter-1 (CAT-1) expression in diabetic animals, which was unaffected by lysine [11].
• However, only in the presence of 0.5 mM/L sodium nitroprusside (SNP) an augmented steady-state CAT-1 mRNA was demonstrated by RT-PCR [11].
• To compare directly the interaction of hCAT-1 and hCAT-2B with neutral amino acids and sodium, we examined the inhibition of these transporters by L-leucine and L-alanine over a wide concentration range [12].
• L-Alanine and L-leucine inhibit uptake by hCAT-2B substantially less completely than uptake by hCAT-1 [12].

Regulatory relationships of SLC7A1

• AMT (100 microM) did not affect L-arginine transport studied by electrophysiological techniques in Xenopus laevis oocytes expressing either the human cationic amino acid transporter hCAT-1 or hCAT-2B [13].

Other interactions of SLC7A1

• Increased expression of SLC7A2/CAT2B is detectable from 3 h of treatment, while SLC7A1 expression is inhibited at later times of incubation [14].
• Immunohistochemistry and Western blotting confirmed the presence of 4F2hc and CAT1 protein in HPMEC [15].
• In association with these biochemical indices, we observed a 38% reduction (P<0.05) in the mRNA expression of the cationic amino acid transporter CAT-1 in ventricular myocardial samples from patients with CHF compared with healthy unused donor myocardium, whereas myocardial NOS enzymatic activity and NOS protein were unchanged [16].
• Pairwise linkage analysis established linkage between ATRC1 and ATP1AL1, D13S1, D13S6, D13S10, D13S11, D13S21, D13S22, D13S33, D13S36, and D13S37 [7].

Analytical, diagnostic and therapeutic context of SLC7A1

• The cytoprotective effect of CAT-1-specific siRNA on ornithine cytotoxicity was measured using quantitative analysis of cellular adenosine triphosphate (ATP) at 24 hours after treatment with ornithine in OAT-deficient RPE cells [2].
• Arginine transport activity, arginine transporter CAT1 mRNA and protein levels were measured with transport assay, Northern blot analysis, and Western blot analysis, respectively [17].
• It suggests a particular temporal code patterning of single LD neuronal firing and its relationships to hippocampal EEG wave code in time series, the latter implies the LD neuronal encoding mechanisms of ATRC-induced epileptic electrical network in bilateral HPCi [18].

References