Ceramides are essential precursors of complex sphingolipids and act as potent signaling molecules. Ceramides are synthesized in the endoplasmic reticulum (ER) and receive their head-groups in the Golgi apparatus, yielding complex sphingolipids (SPs). Transport of ceramides between the ER and the Golgi is executed by the essential ceramide transport protein (CERT) in mammalian cells. However, yeast cells lack a CERT homolog, and the mechanism of ER to Golgi ceramide transport remains largely elusive. Here, we identified a role for yeast Svf1 in ceramide transport between the ER and the Golgi. Svf1 is dynamically targeted to membranes via an N-terminal amphipathic helix (AH). Svf1 binds ceramide via a hydrophobic binding pocket that is located in between two lipocalin domains. We showed that Svf1 membrane-targeting is important to maintain flux of ceramides into complex SPs. Together, our results show that Svf1 is a ceramide binding protein that contributes to sphingolipid metabolism at Golgi compartments.

中文翻译：

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酵母 Svf1 结合神经酰胺并有助于 ER 顺式高尔基体界面处的鞘脂代谢。

神经酰胺是复杂鞘脂的重要前体，可作为有效的信号分子。神经酰胺在内质网 (ER) 中合成，并在高尔基体中接收其头基，产生复杂的鞘脂 (SP)。内质网和高尔基体之间的神经酰胺转运是由哺乳动物细胞中的必需神经酰胺转运蛋白 (CERT) 执行的。然而，酵母细胞缺乏 CERT 同源物，并且 ER 到高尔基体神经酰胺的转运机制在很大程度上仍然难以捉摸。在这里，我们确定了酵母 Svf1 在 ER 和高尔基体之间神经酰胺转运中的作用。Svf1 通过 N 端两亲螺旋 (AH) 动态靶向膜。Svf1 通过位于两个脂质运载蛋白结构域之间的疏水性结合袋结合神经酰胺。我们表明 Svf1 膜靶向对于维持神经酰胺进入复杂 SP 的通量很重要。总之，我们的结果表明 Svf1 是一种神经酰胺结合蛋白，有助于高尔基室的鞘脂代谢。