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Scientific article
English

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

Published inCurrent Biology, vol. 30, p. 3775-3787.e7
Publication date2020
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.

Keywords
  • Sphingolipids
  • Ether lipids
  • Glycosylphosphatidylinositol (GPI)-anchored proteins
  • CRISPR Cas9 screen
  • Systematic lipidomics
  • Early secretory pathway
  • Lipid homeostasis
Citation (ISO format)
JIMENEZ ROJO, Noemi et al. Conserved Functions of Ether Lipids and Sphingolipids in the Early Secretory Pathway. In: Current Biology, 2020, vol. 30, p. 3775–3787.e7. doi: 10.1016/j.cub.2020.07.059
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Identifiers
ISSN of the journal0960-9822
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Creation09/04/2020 12:04:00 PM
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