SLC7A1 Membrane Protein Introduction

Introduction of SLC7A1

SLC7A1 (solute carrier family 7 member 1), also known as CAT-1, ATRC1, ERR or REC1L, is a 63 kD receptor that is associated with the transport of cationic amino acids. Encoded by the gene SLC7A1, the receptor SLC7A1 is classified into SLC7 family which may be divided into two major groups, cationic amino acid transporters (CATs, SLC7A1-4) and glycoprotein-associated amino acid transporters (gpaATs, SLC7A5-11), also called catalytic chains of the hetero(di)meric amino acid transporters (HAT). The SLC7A1 gene is mapped to chromosome 13q12.3 and contains 13 exons encoding a cationic amino acid transporter for arginine and lysine uptake in mammalian cells. There are many transcript variants encoding different isoforms in this gene. It is documented that polypyrimidine tract binding protein (PTB) and heterogeneous nuclear ribonucleoprotein L (hnRNP L) can enhance SLC7A1 mRNA translation through the internal ribosome entry site (IRES) during amino acid starvation, however, activation of protein kinase C (PKC) can down-regulate the expression of cell surface SLC7A1.

Function of SLC7A1 Membrane Protein

As an important member of CATs subgroup, the high-affinity, pH- and sodium-independent transporter SLC7A1 plays key roles in the transport of the cationic amino acids (arginine, lysine and ornithine) in non-hepatic tissues. Furthermore, the L-arginine influx induced by SLC7A1 is indispensable for the inducible nitric oxide synthase (NOS) and arginase enzyme activities, which in turn modulate proliferation and differentiation of human epidermal skin cells. It is also documented that SLC7A1 overexpression in endothelium will counter the ability of oxidative stress to promote pressor responses to behavioural stress. SLC7A1 deficiency has been demonstrated to be associated with abnormal arginine metabolism, reduced endothelial function, and NO production, which may lead to hypertension. MiR-145, targeting SLC7A1, has been recognized as an important factor in the pathogenesis of hypertension. In addition, strong evidence revealed that SLC7A1 may take part in the process of L-ornithine transport at the luminal and abluminal sides of the inner blood-retinal barrier (BRB) and the basal side of the outer BRB. A polymorphism ss52051869 in the 3'UTR of human SLC7A1 is associated with a genetic predisposition to essential hypertension.

Fig.1 Arginine is transported into trophectoderm cells by the solute carrier family member 7 (SLC7A1). (Bazer, 2015)

Application of SLC7A1 Membrane Protein in Literature

1. Wang Y. and Jin L. miRNA-145 is associated with spontaneous hypertension by targeting SLC7A1. Experimental and therapeutic medicine. 2018, 15(1): 548-552. PubMed ID: 29434681
   
   

   The authors studied the specific role of miR-145 in hypertension and they found that silencing miR-145 will induce a significant increase in the SLC7A1 expression and phosphorylated endothelial nitric oxide synthase, indicating that SLC7A1 may be a direct target of miR-145. They also verified that miR-145 functions as a key mediator in the pathogenesis of hypertension via targeting SLC7A1.

2. González M., et al. Insulin-stimulated L-arginine transport requires SLC7A1 gene expression and is associated with human umbilical vein relaxation. Journal of cellular physiology. 2011, 226(11): 2916-2924. PubMed ID: 21302286
   
   

   This article demonstrated that insulin can increase hCAT-1 expression, hCATs-L-arginine transport and maximal transport capacity (V(max) /K(m) ) in insulin-modulated human fetal vascular reactivity. In this process, Sp1 nuclear protein will enrich and bind to SLC7A1 promoter.

3. Yang Z. and Kaye D.M. Mechanistic insights into the link between a polymorphism of the 3′ UTR of the SLC7A1 gene and hypertension. Human mutation. 2009, 30(3): 328-333. PubMed ID: 19067360
   
   

   The authors demonstrated that the major allele of polymorphism ss52051869 in the 3'UTR of human SLC7A1 contains a consensus sequence for the transcription factor SP1 and binds to SP1 however the minor allele fails to bind to SP1. miRNA-122 may bind to the 3'UTR of SLC7A1 and cause the depression of gene expression, contributing to the lesser level of SLC7A1 and the endothelial dysfunction seen in hypertensive subjects.

4. Rajapakse N.W., et al. Endothelial cationic amino acid transporter-1 overexpression blunts the effects of oxidative stress on pressor responses to behavioural stress in mice. Clinical and Experimental Pharmacology and Physiology. 2014, 41(12): 1031-1037. PubMed ID: 25115333
   
   

   The authors used telemetry probes to measure mean arterial pressure (MAP) and they revealed that endothelial CAT-1 overexpression can counter the ability of oxidative stress to augment pressor responses to behavioural stress.

5. Wang X., et al. Functional role of arginine during the peri-implantation period of pregnancy. II. Consequences of loss of function of nitric oxide synthase NOS3 mRNA in ovine conceptus trophectoderm. Biology of reproduction. 2014, 28(7): 2852-63. PubMed ID: 24627544
   
   

   The authors conducted a SLC7A1 mRNA knockdown mediated by morpholino antisense oligonucleotide (MAO) and revealed that arginine is essential for conceptus survival and development, while SLC7A1 is the key transporter of arginine by conceptus trophectoderm (Tr).

SLC7A1 Preparation Options

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Reference

1. Bazer F W, et al. (2015). Select nutrients and their effects on conceptus development in mammals. Animal Nutrition. 1(3), 85-95.

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