ARV1,也称为ACAT相关酶2所需存活1,是一种进化上保守的跨膜蛋白,定位于内质网膜[1]。ARV1在多种生物学过程中发挥着重要作用,包括脂质代谢、细胞凋亡、神经发育和疾病发生[2]。ARV1通过调控脂质分布、脂质合成和脂质代谢相关基因的表达,参与维持细胞内脂质平衡和能量代谢[3]。此外,ARV1还在神经发育中发挥作用,其突变可能导致多种神经系统疾病[4]。
研究发现,ARV1的突变与多种神经系统疾病相关,包括发育和癫痫性脑病(DEE)[5]、共济失调和眼部异常[6]。ARV1突变还可能导致α-胎蛋白水平升高,这在共济失调毛细血管扩张症和共济失调伴眼动不能综合征的诊断中具有重要意义[7]。此外,ARV1的突变还可能影响鞘脂代谢,导致多种神经系统疾病[8]。
研究还发现,ARV1的缺失可能导致小鼠出现瘦弱表型,并伴随能量消耗增加和葡萄糖耐受性改善[9]。这表明ARV1在哺乳动物脂质代谢和能量稳态中发挥重要作用。
综上所述,ARV1是一种重要的跨膜蛋白,在脂质代谢、细胞凋亡、神经发育和疾病发生中发挥着重要作用。ARV1的突变可能导致多种神经系统疾病,包括DEE、共济失调和眼部异常。此外,ARV1的缺失还可能导致小鼠出现瘦弱表型,并伴随能量消耗增加和葡萄糖耐受性改善。进一步研究ARV1的功能和作用机制,有助于深入理解其在生物学过程中的重要作用,并为相关疾病的诊断和治疗提供新的思路和策略。
参考文献:
1. Alazami, Anas M, Patel, Nisha, Shamseldin, Hanan E, Monies, Dorota M, Alkuraya, Fowzan S. 2014. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. In Cell reports, 10, 148-61. doi:10.1016/j.celrep.2014.12.015. https://pubmed.ncbi.nlm.nih.gov/25558065/
2. Kamate, Mahesh, Basavanagowda, Thanuja. 2023. ARV1 Gene: A Novel Cause of Autosomal Recessive Cerebellar Ataxia with Elevated Alpha Fetoprotein. In Cerebellum (London, England), 23, 1239-1244. doi:10.1007/s12311-023-01606-5. https://pubmed.ncbi.nlm.nih.gov/37749428/
3. Ruggles, Kelly V, Garbarino, Jeanne, Liu, Ying, Rader, Dan, Sturley, Stephen L. 2013. A functional, genome-wide evaluation of liposensitive yeast identifies the "ARE2 required for viability" (ARV1) gene product as a major component of eukaryotic fatty acid resistance. In The Journal of biological chemistry, 289, 4417-31. doi:10.1074/jbc.M113.515197. https://pubmed.ncbi.nlm.nih.gov/24273168/
4. Swain, Evelyn, Stukey, Joseph, McDonough, Virginia, Sturley, Stephen L, Nickels, Joseph T. 2002. Yeast cells lacking the ARV1 gene harbor defects in sphingolipid metabolism. Complementation by human ARV1. In The Journal of biological chemistry, 277, 36152-60. doi:. https://pubmed.ncbi.nlm.nih.gov/12145310/
5. Darra, Francesca, Lo Barco, Tommaso, Opri, Roberta, Cantalupo, Gaetano, Guerrini, Renzo. 2021. Migrating Focal Seizures and Myoclonic Status in ARV1-Related Encephalopathy. In Neurology. Genetics, 7, e593. doi:10.1212/NXG.0000000000000593. https://pubmed.ncbi.nlm.nih.gov/34017911/
6. Lagor, W R, Tong, F, Jarrett, K E, Billheimer, J T, Rader, D J. 2015. Deletion of murine Arv1 results in a lean phenotype with increased energy expenditure. In Nutrition & diabetes, 5, e181. doi:10.1038/nutd.2015.32. https://pubmed.ncbi.nlm.nih.gov/26479315/
7. Tinkelenberg, A H, Liu, Y, Alcantara, F, Bard, M, Sturley, S L. . Mutations in yeast ARV1 alter intracellular sterol distribution and are complemented by human ARV1. In The Journal of biological chemistry, 275, 40667-70. doi:. https://pubmed.ncbi.nlm.nih.gov/11063737/
8. Kaliniene, Laura, Šimoliūnas, Eugenijus, Truncaitė, Lidija, Valius, Mindaugas, Meškys, Rolandas. 2017. Molecular Analysis of Arthrobacter Myovirus vB_ArtM-ArV1: We Blame It on the Tail. In Journal of virology, 91, . doi:10.1128/JVI.00023-17. https://pubmed.ncbi.nlm.nih.gov/28122988/
9. Gallo-Ebert, Christina, McCourt, Paula C, Donigan, Melissa, Gygax, Scott E, Nickels, Joseph T. 2011. Arv1 lipid transporter function is conserved between pathogenic and nonpathogenic fungi. In Fungal genetics and biology : FG & B, 49, 101-13. doi:10.1016/j.fgb.2011.11.006. https://pubmed.ncbi.nlm.nih.gov/22142782/