SLC27A2 Membrane Protein Introduction

Introduction of SLC27A2

FATP2 is encoded by SLC27A2 or FATP2 gene and is also known as Very long-chain acyl-CoA synthetase (VLACS, VLCS), Fatty acid transport protein 2 (FATP-2), Fatty-acid-coenzyme A ligase, very long-chain 1, Long-chain-fatty-acid-CoA ligase, EC 6.2.1.3, Solute carrier family 27 member 2 (SLC27A2), THCA-CoA ligase and Very long-chain-fatty-acid-CoA ligase. It belongs to FATP/SLC27 protein family, including cytosolic fatty acid binding proteins and membrane-bound FATPs, which is involved in fatty acid transfer, and is expressed in the placenta.

Function of SLC27A2 Membrane Protein

SLC27A2 is expressed in both plasma membranes of the syncytiotrophoblast of the human placenta, and that SLC27A2 expression in the basal plasma membrane correlated with maternal body mass index. The increased SLC27A2 expression likely facilitates an increased delivery of fatty acids to the fetus in pregnancies complicated by maternal obesity. Protein and mRNA expression analyses revealed that kidney proximal tubules express transmembrane fatty acid transporter-2 (SLC27A2). Kidney SLC27A2 localized exclusively to proximal tubule epithelial cells along the apical but not the basolateral membrane. SLC27A2 knockdown significantly reduced gallbladder triacylglycerol but did not affect key bile composition parameters. Loss of SLC27A2 function not only reduced gallbladder triacylglycerol and reduced the decline in motility associated with lithogenic diets, but also greatly protected animals from gallstone formation. SLC27A2 is a major apical proximal tubule NEFA transporter that regulates lipoapoptosis and may be an amenable target for the prevention of CKD progression. Effective SLC27A2 fatty acid transport inhibitors may represent a key advance in targeting SLC27A2/Slc27a2 fatty acid transport protein to combat diseases associated with lipid overload.

Fig.1 Function and subcellular location of SLC27A2 in fatty acid transport and channeling. (Hardwick, 2013)

Application of SLC27A2 Membrane Protein in Literature

1. Lager S., et al. Protein expression of Fatty acid transporter 2 is polarized to the trophoblast basal plasma membrane and increased in placentas from overweight/obese women. Placenta. 2016, 40:60-66. PubMed ID: 27016784
   
   

   This article reports that the increased SLC27A2 expression could contribute to increased fatty acid delivery to the fetus and the authors in this article speculate that the increased SLC27A2 expression could lead accelerated fetal growth or increased fat deposition.

2. Black P.N., et al. Fatty Acid Transport Proteins: Targeting FATP2 as a Gatekeeper Involved in the Transport of Exogenous Fatty Acids. MedChemComm. 2016, 7(4):612-622. PubMed ID: 27446528
   
   

   This article reveals that Grassofermata is a specific SLC27A2 fatty acid transport inhibitor that has valuable potential to add to our arsenal of pharmaceuticals to prevent and treat lipotoxic disease.

3. Tharp K.M., et al. Prevention of gallbladder hypomotility via FATP2 inhibition protects from lithogenic diet-induced cholelithiasis. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2016, 310(10):G855-G864. PubMed ID: 27033116
   
   

   Authors in this group apply adeno-associated virus-mediated knockdown of the long-chain fatty acid transporter 2 (Slc27A2) to indicate that SLC27A2-driven fatty acid uptake and the subsequent TAG accumulation in gallbladder tissue plays a pivotal role in cholelithiasis, and prevention of this process can protect from gallstone formation, even in the context of supersaturated bile cholesterol levels, thus pointing to new treatment approaches and targets.

4. Su J., et al. Reduced SLC27A2 induces cisplatin resistance in lung cancer stem cells by negatively regulating Bmi1-ABCG2 signaling. Mol. Carcinog. 2015, 55(11):1822-1832. PubMed ID: 26513225
   
   

   This article reports that SLC27A2 expression is reduced in CD166⁺ LCSCs and reduced SLC27A2 correlated chemo-response and poor patient survival. The results of this article indicate that enhanced SLC27A2 expression sensitized CD166⁺ LCSCs to cisplatin by in vitro and in vivo experiments.

5. Khan S., et al. Kidney Proximal Tubule Lipoapoptosis Is Regulated by Fatty Acid Transporter-2 (FATP2). Journal of the American Society of Nephrology. 2018, 29(1):81-91. PubMed ID: 28993506
   
   

   This article concludes that SLC27A2 is a major apical proximal tubule NEFA transporter that regulates lipoapoptosis and may be an amenable target for the prevention of CKD progression.

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Reference

1. Hardwick J P., et al. (2013) Eicosanoids in Metabolic Syndrome. Advances in pharmacology (San Diego, Calif.). 66:157-266.

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