Ikeda Atsuko, Schlarmann Philipp, Kurokawa Kazuo, Nakano Akihiko, Riezman Howard, Funato Kouichi
Graduate School of Biosphere Science, Hiroshima University, Kagamiyama 1-4-4, Higashi-Hiroshima 739-8528, Japan.
Live Cell Super-Resolution Imaging Research Team, RIKEN Center for Advanced Photonics, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
iScience. 2020 Oct 7;23(10):101603. doi: 10.1016/j.isci.2020.101603. eCollection 2020 Oct 23.
Lipid composition varies among organelles, and the distinct lipid composition is important for specific functions of each membrane. Lipid transport between organelles, which is critical for the maintenance of membrane lipid composition, occurs by either vesicular or non-vesicular mechanisms. In yeast, ceramide synthesized in the endoplasmic reticulum (ER) is transported to the Golgi apparatus where inositolphosphorylceramide (IPC) is formed. Here we show that a fraction of Tcb3p, a yeast tricalbin protein, localizes to ER-Golgi contact sites. Tcb3p and their homologs Tcb1p and Tcb2p are required for formation of ER-Golgi contacts and non-vesicular ceramide transport. Absence of Tcb1p, Tcb2p, and Tcb3p increases acylceramide synthesis and subsequent lipid droplet (LD) formation. As LD can sequester excess lipids, we propose that tricalbins act as regulators of ceramide transport at ER-Golgi contact sites to help reduce a potentially toxic accumulation of ceramides.
细胞器之间的脂质组成各不相同，独特的脂质组成对于每个膜的特定功能很重要。细胞器之间的脂质转运对于维持膜脂质组成至关重要，其通过囊泡或非囊泡机制发生。在酵母中，在内质网（ER）中合成的神经酰胺被转运到高尔基体，在那里形成肌醇磷酸神经酰胺（IPC）。在这里，我们表明酵母三聚体蛋白Tcb3p的一部分定位于内质网-高尔基体接触位点。Tcb3p及其同源物Tcb1p和Tcb2p是内质网-高尔基体接触形成和非囊泡神经酰胺转运所必需的。缺乏Tcb1p、Tcb2p和Tcb3p会增加酰基神经酰胺的合成以及随后脂滴（LD）的形成。由于脂滴可以隔离过量的脂质，我们提出三聚体蛋白在内质网-高尔基体接触位点作为神经酰胺转运的调节因子，以帮助减少神经酰胺潜在的毒性积累。
