Regulation and Transport Mechanism of Choline Transporter-Like Protein 1 (CTL1/SLC44A1)

作为一种必需的营养素，胆碱主要用于膜磷脂的生物合成。一些胆碱在线粒体中被氧化成甜菜碱，只有少量的胆碱用于乙酰胆碱的合成。胆碱是带正电荷的季胺，需要蛋白质介导的转运才能通过膜。我们最近发现，胆碱转运蛋白样蛋白1（CTL1）作为胆碱转运蛋白在质膜和线粒体的功能。CTL1的功能取决于细胞分化状态和胆碱含量。胆碱缺乏会降低CTL1水平，导致膜合成受损并增加脂滴的积累。胆碱添加刺激CTL1基因表达并恢复其转运功能。关于CTL1的调控和转运机制还有许多未知数。我们计划阐明：

As an essential nutrient, choline is mostly consumed for the biosynthesis of membrane phospholipids. Some choline is oxidised in mitochondria to betaine and only small amount of choline is used for acetylcholine synthesis. Choline is positively charged quaternary amine and requires a protein-mediated transport to pass the membranes. We recently established that choline-transporter-like protein 1 (CTL1) function as a choline transporter at the plasma membrane and mitochondria. CTL1 function depends on cell differentiation state and choline content. Choline deficiency reduces CTL1 levels, causing impairments in the membrane synthesis and increasing accumulation of lipid droplets. Choline addition stimulates CTL1 gene expression and restores its transport function. There are multiple unknowns about the CTL1 regulation and transport mechanism. We plan to elucidate: