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  • Conserved Functions of Ether Lipids and Sphingolipids in the Early Secretory Pathway.

Conserved Functions of Ether Lipids and Sphingolipids in the Early Secretory Pathway.

Current biology : CB (2020-08-29)
Noemi Jiménez-Rojo, Manuel D Leonetti, Valeria Zoni, Adai Colom, Suihan Feng, Namrata R Iyengar, Stefan Matile, Aurélien Roux, Stefano Vanni, Jonathan S Weissman, Howard Riezman
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

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Agarose, Ultra-low Gelling Temperature, molecular biology grade
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Oleoyl chloride, ≥89%
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Myriocin from Mycelia sterilia, ≥98% (HPLC), powder
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