SLC43A1 Membrane Protein Introduction

Introduction of SLC43A1

SLC43A1 is encoded by the SLC43A1 gene which is located on 11p11.1-p11.2. The expression of the gene is up-regulated in human prostate cancer, and a unique splice variant mRNA is found to primarily associate with fetal tissues and tumors. SLC43A1 belongs to the SLC43A transporter (TC 2.A.1.44) family of which members are Na+-independent, system-L like amino acid transporters. The molecular mass of SLC43A1 is about 61 kDa.

Function of SLC43A1 Membrane Protein

SLC43A1 is a multi-pass membrane protein. The main biological function of SLC43A1 is high-affinity transport of large neutral amino acids by a sodium-independent way. It also plays an important role in L-amino acid transmembrane transport. The expression of SLC43A1 in adults is different from the fetus, it can be detected in all tissues examined with the highest expression in the pancreas in adults. In the fetus, the highest expression in the liver and lower levels in the kidney, and lung. Accordingly, SLC43A1 is highly expressed in prostate cancer cells, and it is associated with the development of prostate cancer, from prostatic intraepithelial neoplasia to invasive prostate cancer. LAT3/SLC43A1 can regulate Leucine uptake which is related to mTORC1 activation in prostate cancer cells, and mTORC1 functions in protein translation and cell growth. Beyond that, SLC43A1 is found to especially expressed in the apical side of the plasma membrane of the podocyte foot processes. SLC43A1 is crucial for the development and maintenance of podocyte structure and function by regulating the actin cytoskeleton and protein synthesis.

Fig.1 LAT3/SLC43A1 and its inhibitor ESK246 function in mTORC1 signal pathway (Wang, 2014).

Application of SLC43A1 Membrane Protein in Literature

1. Sekine Y., et al. Amino acid transporter LAT3 is required for podocyte development and function. Journal of the American Society of Nephrology: JASN. 2009. PubMed ID: 19443642
   
   

   This article is about the tissue distribution and physiologic function of LAT3/SLC43A1. LAT3/SLC43A1 localizes to the apical plasma membrane of podocyte foot processes, and functions in the development and maintenance of podocyte structure.

2. Wang Q., et al. Monoterpene Glycoside ESK246 from Pittosporum Targets LAT3 Amino Acid Transport and Prostate Cancer Cell Growth. Acs Chemical Biology. 2014, 9(6):1369-1376. PubMed ID: 24762008
   
   

   This article reveals that LAT3/SLC43A1 can regulate the uptake of the Leucin which is critical for mTORC1 signaling leading to protein translation. And the authors find an inhibitor of the SLC43A1, ESK246 which is a monoterpene glycoside. It can be used to study LAT3 function and upon which new anti-prostate cancer therapies may be based.

3. Bodoy S., et al. The small SLC43 family: facilitator system l amino acid transporters and the orphan EEG1. Molecular Aspects of Medicine. 2013, 34(2-3):638-645. PubMed ID: 23268354
   
   

   Authors in this review focus on the physiological roles of the SLC43 family. Morphants suggested the importance of LAT3 in renal podocyte development in zebrafish. LAT3 also plays a role in the flux of branched-chain amino acids (BCAAs) from liver and skeletal muscle to the bloodstream. Besides, LAT3 is up-regulated in androgen-dependent cancers.

4. Cole K.A., et al. cDNA Sequencing and Analysis of POV1 (PB39): A Novel Gene Up-regulated in Prostate Cancer. Genomics. 1998, 51(2):282-287. PubMed ID: 9722952
   
   

   Authors of this article firstly identify SLC43A1/POV1 gene and then they also study the association of SLC43A1 cDNA sequence with the murine sequence. The article finally reveals that SLC43A1/POV1 plays a role in the development of human prostate cancer.

5. Babu E., et al. Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters. Journal of Biological Chemistry. 2003, 278(44):43838. PubMed ID: 12930836
   
   

   In this article, SLC43A1/LAT3 is identified as a transporter subserving system L2 according to the substrate selectivity, affinity, and N-ethylmaleimide sensitivity. The authors reveal that SLC43A1/LAT3 should denote a new family of organic solute transporters.

SLC43A1 Preparation Options

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Reference

1. Wang Q., et al. (2014). Monoterpene glycoside esk246 from pittosporum targets lat3 amino acid transport and prostate cancer cell growth. Acs Chemical Biology, 9(6), 1369-1376.

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