Slc1a3-KO Mouse

Slc1a3, also known as the glutamate/aspartate transporter, is a member of the glutamate transporter family. It plays a crucial role in regulating the transport of glutamate and aspartate, which are involved in various cellular processes, such as neurotransmission, metabolism, and cell signaling [3,4]. Glutamate is a key neurotransmitter in the central nervous system, and its proper regulation is essential for normal brain function. Additionally, Slc1a3 may be associated with pathways like the PI3K/AKT signaling pathway [3].

In terms of disease-related findings, knockdown of Slc1a3 inhibited Newcastle disease virus (NDV) infection. It was found that NDV hijacks Slc1a3 to regulate glutamine catabolism for its efficient replication, as Slc1a3 knockdown reduced glutamate levels and glutaminolysis [1]. In gastric cancer, Slc1a3 was overexpressed, and this overexpression was associated with poor prognosis. In vitro and in vivo assays showed that Slc1a3 affected glucose metabolism and promoted gastric cancer growth via the PI3K/AKT pathway [3]. In solid tumors, SLC1A3 inhibition in combination with L-asparaginase (ASNase) caused cell cycle arrest or apoptosis, indicating its role in ASNase resistance [4]. In hepatocellular carcinoma (HCC), Slc1a3 overexpression was associated with a poor prognosis, and it promoted HCC cell motility and invasion by modifying immune responses and epithelial-mesenchymal transition [6]. In osimertinib-resistant EGFR mutant lung cancer cells, inhibition of Slc1a3 increased osimertinib sensitivity, and combined inhibition of Slc1a3 and glutaminase showed potential in overcoming resistance [8]. Also, SLC1A3 has been suggested as a potential diagnostic marker for diabetic nephropathy as it was identified as an up-regulated hub gene with excellent diagnostic efficacy [2]. Moreover, recent studies have implicated SLC1A3 in hemiplegic migraine, though the exact role is yet to be fully understood [5,7].

In conclusion, Slc1a3 is an important gene involved in multiple biological processes, especially in regulating the metabolism of key amino acids and their related functions. Its dysregulation has been linked to various diseases, including viral infections, different types of cancers, and potentially migraine-related disorders. The findings from functional studies, such as knockdown experiments, in these disease models have provided valuable insights into the role of Slc1a3, which may help in developing new therapeutic strategies for these diseases.

References:

1. Liu, Panrao, Tang, Ning, Meng, Chunchun, Lin, Shu-Hai, Ding, Chan. . SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism. In Virulence, 13, 1407-1422. doi:10.1080/21505594.2022.2112821. https://pubmed.ncbi.nlm.nih.gov/35993169/

2. Xu, Mingming, Zhou, Hang, Hu, Ping, Liu, Li, Liu, Xiaoqiang. 2023. Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning. In Frontiers in immunology, 14, 1084531. doi:10.3389/fimmu.2023.1084531. https://pubmed.ncbi.nlm.nih.gov/36911691/

3. Xu, Liyi, Chen, Jiamin, Jia, Litao, Awaleh Moumin, Faycal, Cai, Jianting. 2020. SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway. In Journal of cellular and molecular medicine, 24, 14392-14404. doi:10.1111/jcmm.16060. https://pubmed.ncbi.nlm.nih.gov/33145952/

4. Sun, Jianhui, Nagel, Remco, Zaal, Esther A, Berkers, Celia R, Agami, Reuven. 2019. SLC1A3 contributes to L-asparaginase resistance in solid tumors. In The EMBO journal, 38, e102147. doi:10.15252/embj.2019102147. https://pubmed.ncbi.nlm.nih.gov/31523835/

5. Nandyala, Arathi, Shah, Tulsi, Ailani, Jessica. 2023. Hemiplegic Migraine. In Current neurology and neuroscience reports, 23, 381-387. doi:10.1007/s11910-023-01277-z. https://pubmed.ncbi.nlm.nih.gov/37247170/

6. Zhi, Renhou, Fan, Fan. 2024. SLC1A3 is a novel prognostic biomarker associated with immunity and EMT in hepatocellular carcinoma. In Discover oncology, 15, 676. doi:10.1007/s12672-024-01561-5. https://pubmed.ncbi.nlm.nih.gov/39560677/

7. Paucar, Martin, Granberg, Tobias, Lagerstedt-Robinson, Kristina, Nordin, Love, Svenningsson, Per. 2020. SLC1A3 variant associated with hemiplegic migraine and acetazolamide-responsive MRS changes. In Neurology. Genetics, 6, e474. doi:10.1212/NXG.0000000000000474. https://pubmed.ncbi.nlm.nih.gov/32754645/

8. Ochi, Nobuaki, Miyake, Noriko, Takeyama, Masami, Kiura, Katsuyuki, Takigawa, Nagio. 2024. The combined inhibition of SLC1A3 and glutaminase in osimertinib-resistant EGFR mutant cells. In Biochimica et biophysica acta. General subjects, 1868, 130675. doi:10.1016/j.bbagen.2024.130675. https://pubmed.ncbi.nlm.nih.gov/39059510/