Numerous biological processes are regulated by the intercellular communications arising from extracellular vesicles (EVs) released from cells. However, the mechanisms that regulate the quantity of EV discharged have yet to be understood. While it is known that ATP9A, a P4-ATPase, is involved in endosomal recycling, it is not clear whether it also contributes to the release of EVs and the makeup of exosomal lipids. This study is aimed at exploring the role of human ATP9A in the process of EV release and, further, to analyze the profiles of EV lipids regulated by ATP9A. Our results demonstrate that ATP9A is located in both the intracellular compartments and the plasma membrane. The percentage of ceramides and sphingosine was found to be significantly greater in the control cells than in the ATP9A overexpression and ATP9A knockout groups. However, EV release was greater in ATP9A knockout cells, indicating that ATP9A inhibits the release of EVs. This study revealed the effects of ATP9A on the release of EVs and the lipid composition of exosomes.

中文翻译：

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ATP9A对细胞外囊泡释放和脂质体脂质成分的影响

许多生物过程受细胞释放的细胞外囊泡（EV）引起的细胞间通讯的调节。但是，调节EV排放量的机制尚待了解。虽然已知ATP9A（一种P4-ATPase）参与了内体循环，但尚不清楚它是否也有助于EV的释放和外泌体脂质的形成。这项研究旨在探讨人ATP9A在EV释放过程中的作用，并进一步分析由ATP9A调节的EV脂质的分布。我们的结果表明，ATP9A位于细胞内区室和质膜中。发现在对照细胞中神经酰胺和鞘氨醇的百分比显着大于ATP9A过表达和ATP9A敲除组中的百分比。然而，ATP9A敲除细胞中的EV释放更大，表明ATP9A抑制了EV的释放。这项研究揭示了ATP9A对EV释放和外泌体脂质组成的影响。