Trifunctional Sphinganine: A New Tool to Dissect Sphingolipid Function,ACS Chemical Biology

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Trifunctional Sphinganine: A New Tool to Dissect Sphingolipid Function
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2024-01-29 , DOI: 10.1021/acschembio.3c00554
Scotland Farley _{1,

2} , Frank Stein ₃ , Per Haberkant ₃ , Fikadu G Tafesse ₂ , Carsten Schultz ₁

Affiliation

Functions and cell biology of the sphingolipids sphingosine and sphinganine in cells are not well understood. While some signaling roles for sphingosine have been elucidated, the closely related sphinganine has been described only insofar as it does not elicit many of the same signaling responses. Here, we prepared multifunctionalized derivatives of the two lipid species that differ only in a single double bond of the carbon backbone. Using these novel probes, we were able to define their spatiotemporal distributions within cells. Furthermore, we used these tools to systematically map the protein interactomes of both lipids. The lipid–protein conjugates, prepared through photo-crosslinking in live cells and extraction via click chemistry to azide beads, revealed significant differences in the captured proteins, highlighting their distinct roles in various cellular processes. This work elucidates mechanistic differences between these critical lipids and sets the foundation for further studies of the cellular functions of sphingosine and sphinganine.

中文翻译：

三功能二氢鞘氨醇：剖析鞘脂功能的新工具

细胞中鞘脂类鞘氨醇和二氢鞘氨醇的功能和细胞生物学尚不清楚。虽然鞘氨醇的一些信号传导作用已被阐明，但密切相关的二氢鞘氨醇仅在其不引起许多相同的信号传导反应的范围内被描述。在这里，我们制备了两种脂质种类的多功能衍生物，它们仅在碳主链的单个双键上有所不同。使用这些新颖的探针，我们能够定义它们在细胞内的时空分布。此外，我们使用这些工具系统地绘制了两种脂质的蛋白质相互作用组图。通过活细胞中的光交联制备脂质-蛋白质缀合物，并通过点击化学提取叠氮珠，揭示了捕获的蛋白质的显着差异，突出了它们在各种细胞过程中的独特作用。这项工作阐明了这些关键脂质之间的机制差异，并为进一步研究鞘氨醇和二氢鞘氨醇的细胞功能奠定了基础。

更新日期：2024-01-29

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