SLC38A1 Membrane Protein Introduction

Introduction of SLC38A1

System N/A neutral amino acid transporter (SNAT, SLC38A1) is a family of transporters involved in transferring neutral and aliphatic amino acids across the cell membrane. The SNAT family is also called SLC38 family. The transporters in this family are responsible for either system A or system N transport. SLC38A1 belongs to system A subfamily, meaning that this protein is exclusively Na⁺ dependent. It couples amino acid transport to the Na⁺ electrochemical potential gradient with 1:1 stoichiometry. Moreover, it could be inhibited by the amino acid analog 2-methylamino-isobutyric acid (MeAIB). Hydropathy analysis predicts that SLC38A1 has 11 membrane-spanning domains. The tissue distribution of this transporter includes the brain, retina, heart, placenta, adrenal gland. Primarily, it is expressed in neuronal cells of the brain, axons of ganglion cells in the nerve fiber, and optic nerves of the retina. SLC38A1 preferentially transports L-glutamine (Gln) followed by L-histidine and L-alanine.

Functions of SLC38A1 Membrane Protein

Various physiological studies and pathological studies have revealed the involvement of SLC38A1. Firstly, SLC38A1 has been postulated to play a critical role in Gln-glutamate recycling and in the generation of neurotransmitters. Additionally, the stimulation of neuronal differentiation associated with the enhancement of dendritic development by brain-derived neurotrophic factor requires the up-regulation of SLC38A1 expression. The low expression of SLC38A1 has been reported to be associated with suicidal behavior. Many studies have demonstrated that SLC38A1 played a potential role in cancer development and progression, including hepatocellular carcinoma, breast cancer, osteosarcoma, and cholangiocarcinoma. As a result, SLC38A1 might serve as a prognostic and therapeutic marker of these cancers or tumor diseases.

Fig.1 Proposed structure of human SNAT1.

Application of SLC38A1 Membrane Protein in Literature

1. Jin L.W., et al. Dysregulation of glutamine transporter SNAT1 in Rett syndrome microglia: a mechanism for mitochondrial dysfunction and neurotoxicity. Journal of Neuroscience. 2015, 35(6): 2516-2529. PubMed ID: 25673846
   
   

   This study characterized the role of SLC38A1, which was a MeCP2 target gene, in microglia to understand the mechanism of microglia dysfunction in Rett syndrome. The results suggested a therapeutic potential of mitochondria-targeted antioxidants for Rett syndrome.

2. Iyer R.P., et al. N-Glycosylation influences transport, but not cellular trafficking, of a neuronal amino acid transporter SNAT1. Biochemical Journal. 2016, 473(22): 4227-4242. PubMed ID: 27655909
   
   

   This study investigated the N-glycosylation of SNAT1 and the importance of N-glycosylation for SNAT1 function. The results showed that there were three de novo glycosylation sites and this modification might play an important role in the transport of substrates across the cell membrane.

3. Dikalova A., et al. Sodium-coupled neutral amino acid transporter 1 (SNAT1) modulates L-citrulline transport and nitric oxide (NO) signaling in piglet pulmonary arterial endothelial cells. PloS one. 2014, 9(1): e85730. PubMed ID: 24454923
   
   

   This study investigated the functional link between the SNATs, L-citrulline, and NO signaling using the siRNA technique. The results showed that SNAT1 mediated L-citrulline transport modulated eNOS coupling and thus regulated NO production in hypoxic PAECs from newborn piglets, suggesting that increasing the SNAT1-mediated L-citrulline might be potential therapeutic strategies to enhance NO production in patients with pulmonary vascular diseases.

4. Wang K., et al. Activation of SNAT1/SLC38A1 in human breast cancer: correlation with p-Akt overexpression. BMC cancer. 2013, 13(1): 343. PubMed ID: 23848995
   
   

   This study investigated SNAT1 expression in breast cancers and explored the underlying mechanism of this protein in promoting breast carcinogenesis using RT-PCR, Western blotting, and tissue microarray. Results showed that the correlation of SANT1 with Akt signaling might play a critical role in the development and progression of breast cancer.

5. Bröer A., et al. Deletion of amino acid transporter ASCT2 (SLC1A5) reveals an essential role for transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to sustain glutaminolysis in cancer cells. Journal of biological chemistry. 2016, 291(25): 13194-205. PubMed ID: 27129276
   
   

   Using Hela epithelial cervical cancer cells and 143B osteosarcoma cells that expressed glutamine transporters such as SNAT1, this study investigated the role of these transporters for glutaminolysis. The results showed that the expression of SNAT1 and SNAT2 were required for glutamine uptake.

SLC38A1 Preparation Options

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