SLC44A2 Membrane Protein Introduction

Introduction of SLC44A2

Solute carrier family 44 member 2 (SLC44A2), also known as choline transporter-like protein 2 (CTL2), is a transmembrane protein that in human is encoded by SLC44A1 gene. It is a member of the choline transporter-like (CTL) family and is functionally expressed as choline transporters. In humans, SLC44A2 mRNA and protein are found in the inner ear, trophoblastic cells, brain microvascular endothelial cells, glioblastoma cells, and tongue cancer cells. The intracellular localization of CTL2 is in the plasma membrane and mitochondria.

Function of SLC44A2 Membrane Protein

The choline transport system has been assorted into three transporter families, including choline transporter-like proteins (CTLs), high-affinity choline transporter 1 (CHT1), and polyspecific organic cation transporters (OCTs). The CTL family consists of five members: CTL1, CTL2, CTL3, CTL4, CTL5. Recently, it has been proved that CTL2 exhibits detectable choline transport activity. However, the physiological function of CTL2 has not been fully characterized and the Km values for choline are still unknown. Choline is considered as a key substance for mitochondria since the deficiency of choline leads to mitochondrial and cellular oxidative injury as well as lipid peroxidation. CTL2 might play a role in choline uptake in mitochondria, which is the rate-limiting step in SAM (S-adenosyl-L-methionine) synthesis and DNA methylation. Thus, researchers hypothesize that CTL2 may be the predominant site for the control of choline oxidation in mitochondria and might be essential molecules of the apoptotic cell death in esophageal cancer cells. Furthermore, identification of the CTL2-mediated choline transport system may provide a potential novel target for esophageal cancer therapy.

Fig.1 Predicted structure of hCTL2. (Nair, 2004)

Application of SLC44A2 Membrane Protein in Literature

1. Nagashima F., et al. Molecular and functional characterization of choline transporter-like proteins in esophageal cancer cells and potential therapeutic targets. Biomol Ther (Seoul). 2018, 26(4):399-408. PubMed ID: 29223141
   
   

   The results of this study show that the identification of the CTL2-mediated choline transport system may provide a potential novel target for esophageal cancer therapy.

2. Iwao B., et al. Functional expression of choline transporter like-protein 1 (CTL1) and CTL2 in human brain microvascular endothelial cells. Neurochem Int. 2016, 93:40-50. PubMed ID: 26746385
   
   

   This article suggests that choline is primarily transported by an intermediate-affinity choline transport system, CTL1 and CTL2, in hBMECs.

3. Bayat B., et al. Choline transporter-like protein-2: New von Willebrand factor-binding partner involved in antibody-mediated neutrophil activation and transfusion-related acute lung injury. Arterioscler Thromb Vasc Biol. 2015, 35(7):1616-22. PubMed ID: 25931511
   
   

   Authors of this study identify CTL-2 as a new binding partner for VWF (von Willebrand factor).

4. Bougie D.W., et al. Transfusion-related acute lung injury-associated HNA-3a antibodies recognize complex determinants on choline transporter-like protein 2. Transfusion. 2014, 54(12):3208-15. PubMed ID: 24846273
   
   

   Authors of this study characterize reactions of HNA-3a antibodies, which can cause severe, sometimes fatal, transfusion-related acute lung injury when present in transfused blood, against recombinant versions of human, mouse, and human/mouse (chimeric) CTL2.

5. Kanack A.J., et al. Full-length recombinant choline transporter-like protein 2 containing arginine 154 reconstitutes the epitope recognized by HNA-3a antibodies. Transfusion. 2012, 52(5):1112-6. PubMed ID: 22032286

   Results of this article prove that R154 in the context of full-length CTL2 is both necessary and sufficient to create the HNA-3a epitope, a target for antibodies that cause severe transfusion-related acute lung injury.

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Reference

1. Nair T S, et al. (2004). Identification and characterization of choline transporter-like protein 2, an inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced hearing loss. Journal of Neuroscience. 24(7), 1772-1779.

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