Conserved Functions of Ether Lipids and Sphingolipids in the Early Secretory Pathway
Conserved Functions of Ether Lipids and Sphingolipids in the Early Secretory Pathway
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DOI：
10.1016/j.cub.2020.07.059
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发表时间：
2020-10-05
期刊：
影响因子：
9.2
通讯作者：
Riezman, Howard
中科院分区：
文献类型：
--
作者：
Jimenez-Rojo, Noemi;Leonetti, Manuel D.;Riezman, Howard
Sphingolipids play important roles in physiology and cell biology, but a systematic examination of their functions is lacking. We performed a genome-wide CRISPRi screen in sphingolipid-depleted human cells and identified hypersensitive mutants in genes of membrane trafficking and lipid biosynthesis, including ether lipid synthesis. Systematic lipidomic analysis showed a coordinate regulation of ether lipids with sphingolipids, suggesting an adaptation and functional compensation. Biophysical experiments on model membranes show common properties of these structurally diverse lipids that also share a known function as glycosylphosphatidylinositol (GPI) anchors in different kingdoms of life. Molecular dynamics simulations show a selective enrichment of ether phosphatidylcholine around p24 proteins, which are receptors for the export of GPI-anchored proteins and have been shown to bind a specific sphingomyelin species. Our results support a model of convergent evolution of proteins and lipids, based on their physico-chemical properties, to regulate GPI-anchored protein transport and maintain homeostasis in the early secretory pathway.
