SLC43A2 Membrane Protein Introduction

Introduction of SLC43A2

SLC43A2 is encoded by the SLC43A2 gene which is located on 17p13.3. The molecular mass of SLC43A2 is about 60 kDa. The overexpression of LAT4 in tumor cells and xenografts has been detected. It is a member of system L amino acid transporters which can mediate the movement of bulky neutral amino acids across cell membranes. There are another three proteins that induce system L activity: LAT1, LAT2, and LAT3. LAT1 and LAT2 belong to the solute carrier family 7 (SLC7), while LAT3 and LAT4 belong to SLC43.

Function of SLC43A2 Membrane Protein

SLC43A2 is identified as a system L amino acid transporter primarily. Human SLC43A2 exhibits 57% identity to human SLC43A1. Just like SLC43A1, the amino acid transport activity of LAT4 is also sodium-, chloride- and pH-independent. SLC43A2 is highly expressed in kidney, placenta and peripheral blood leukocytes, it expresses in epithelial cells of the distal tubule and collecting duct in the kidney. It can be detected mainly in epithelial cells in the base of the villus and crypt cells of the intestinal microvilli in the intestine. Besides, SLC43A2 has a narrow substrate selectivity, it prefers to bind leucine, isoleucine, and phenylalanine. SLC43A2 acts as a uniporter with symmetric intracellular and extracellular apparent affinities for phenylalanine in the Xenopus oocyte expression system. Accordingly, SLC43A2 is a basolateral uniporter for essential neutral amino acids in the small intestine and kidney tubule, it is necessary for early nutrition and development. Beyond that, it has been shown that SLC43A2 will be upregulated in the liver and skeletal muscle upon starvation.

Fig.1 Apical and basolateral amino acid transporter cooperation in proximal tubule kidney cell (Guetg, 2015).

Application of SLC43A2 Membrane Protein in Literature

1. Guetg A., et al. Essential amino acid transporter Lat4 (Slc43a2) is required for mouse development. Journal of Physiology. 2015, 593(5):1273-89. PubMed ID: 25480797
   
   

   Authors in this article focus on the physiological role and subcellular localization of LAT4/SLC43A2. They use knockout mice model to solve the problem. They reveal that Lat4 is localized at the basolateral side of (re)absorbing epithelia and it is a symmetrical uniporter for neutral essential AAs, SLC43A2 is necessary for early nutrition and development.

2. Bodoy S., et al. Identification of LAT4, a novel amino acid transporter with system L activity. Journal of Biological Chemistry. 2005, 280(12):12002-11. PubMed ID: 15659399
   
   

   In this article, SLC43A2 is identified as a system L amino acid transporter for the first time. This article also reveals that SLC43A2 is expressed in the epithelial cells of the distal tubule and the collecting duct in the kidney, and in the intestine, SLC43A2 is mainly present in the cells of the crypt.

3. Haase C., et al. L-type amino acid transporters LAT1 and LAT4 in cancer: uptake of 3-O-methyl-6-18F-fluoro-L-dopa in human adenocarcinoma and squamous cell carcinoma in vitro and in vivo. Journal of Nuclear Medicine. 2007, 48(12):2063-2071. PubMed ID: 18056335
   
   

   Authors in this group intend to prove that F-labeled amino acids that accumulate in tumors via LAT represent an important class of imaging agents for visualization of tumors in vivo by PET. In poorly differentiated squamous cell head and neck carcinoma with increased LAT1 and LAT4/SLC43A2 expression, 18F-OMFD can be a suitable tracer for diagnostic imaging of amino acid transport.

4. Gazouli M., et al. Transferable class C beta-lactamases in Escherichia coli strains isolated in Greek hospitals and characterization of two enzyme variants (LAT-3 and LAT-4) closely related to Citrobacter freundii AmpC beta-lactamase. J Antimicrob Chemother. 1998, 42(4):419-25.
   
   

   This article reveals that the LAT-3 and LAT-4-lactamases are variants of the AmpC β-lactamase of C. freundii. The variation in production of the LAT-3 and LAT-4 enzymes expressed from the E. coli strains is of interest.

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Reference

1. Guetg A., et al. (2015). Essential amino acid transporter lat4 (slc43a2) is required for mouse development. Journal of Physiology, 593(5), 1273-89.

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