Slc38a2,也称为SNAT2(Sodium-Coupled Neutral Amino Acid Transporter 2),是一种重要的中性氨基酸转运蛋白。Slc38a2属于SLC(Solute Carrier)家族,负责细胞内外中性氨基酸的转运,这对于维持细胞内氨基酸的稳态至关重要。Slc38a2在多种细胞类型中广泛表达,包括神经元、肾髓质集合管细胞、胎盘滋养层细胞等。其功能涉及氨基酸的摄取、代谢、信号传导等多个方面。
在神经系统,Slc38a2的异常表达与帕金森病(PD)的发生发展密切相关。研究发现,Slc38a2的基因表达上调可以减轻PD症状,这可能是通过调节GABA能突触通路和cAMP信号通路实现的[1]。此外,Slc38a2还可以通过mTORC1信号通路保护肾髓质免受高渗性诱导的铁死亡,维持细胞内环境的稳定[2]。
在免疫系统中,Slc38a2的表达水平与CD8+ T细胞命运的决定有关。研究表明,Slc38a2可以抑制记忆性T细胞(TMEM)的分化,部分是通过调节mTORC1信号通路实现的[3]。此外,Slc38a2的基因敲除可以导致小鼠的胎仔生长受限,这可能是由于胎盘滋养层细胞对氨基酸的摄取减少导致的[4]。
在肿瘤发生发展中,Slc38a2也发挥着重要作用。研究发现,miR-10b-5p可以通过靶向Slc38a2促进肝细胞癌的生长和转移,这可能是通过调节细胞代谢实现的[5]。此外,Slc38a2的表达上调可以增强肺癌细胞对谷氨酰胺的摄取,进而促进肿瘤的生长和转移[6]。
综上所述,Slc38a2作为一种重要的中性氨基酸转运蛋白,在神经系统、免疫系统、肿瘤发生发展中发挥着重要作用。Slc38a2的表达和功能异常与多种疾病的发生发展密切相关,因此,Slc38a2可能成为治疗这些疾病的潜在靶点。
参考文献:
1. Bian, Li-Hua, Yao, Zi-Wei, Wang, Zhe-Yi, Shi, Jin-Li, Guo, Jian-You. 2022. Nardosinone regulates the slc38a2 gene to alleviate Parkinson's symptoms in rats through the GABAergic synaptic and cAMP pathways. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 153, 113269. doi:10.1016/j.biopha.2022.113269. https://pubmed.ncbi.nlm.nih.gov/35728354/
2. Du, Chunxiu, Xu, Hu, Cao, Cong, Guan, Youfei, Zhang, Xiaoyan. 2023. Neutral amino acid transporter SLC38A2 protects renal medulla from hyperosmolarity-induced ferroptosis. In eLife, 12, . doi:10.7554/eLife.80647. https://pubmed.ncbi.nlm.nih.gov/36722887/
3. Huang, Hongling, Zhou, Peipei, Wei, Jun, Yu, Jiyang, Chi, Hongbo. 2021. In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions. In Cell, 184, 1245-1261.e21. doi:10.1016/j.cell.2021.02.021. https://pubmed.ncbi.nlm.nih.gov/33636132/
4. Vaughan, Owen R, Maksym, Katarzyna, Silva, Elena, Powell, Theresa L, Jansson, Thomas. . Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice. In Clinical science (London, England : 1979), 135, 2049-2066. doi:10.1042/CS20210575. https://pubmed.ncbi.nlm.nih.gov/34406367/
5. Xia, Mingzhi, Chen, Jie, Hu, Yingyun, Bu, Qianqian, Shen, Haoming. 2024. miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2. In Cancer biology & therapy, 25, 2315651. doi:10.1080/15384047.2024.2315651. https://pubmed.ncbi.nlm.nih.gov/38390840/
6. Liu, Tongyan, Han, Chencheng, Fang, Panqi, Hu, Zhibin, Yin, Rong. 2022. Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake in lung adenocarcinoma. In Journal of hematology & oncology, 15, 141. doi:10.1186/s13045-022-01359-4. https://pubmed.ncbi.nlm.nih.gov/36209111/