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Conserved functions of ether lipids and sphingolipids in the early secretory pathway

  • Jiménez-Rojo, Noemi NCCR Chemical Biology, Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland -
  • Leonetti, Manuel D. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA - Howard Hughes Medical Institute, San Francisco, CA 94158, USA -
  • Zoni, Valeria Department of Biology, University of Fribourg, Fribourg, Switzerland
  • Colom, Adai NCCR Chemical Biology, Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland
  • Feng, Suihan NCCR Chemical Biology, Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland
  • Iyengar, Namrata R. Institute of Protein Biochemistry (IBP), Italian National Research Council (CNR), Napoli, Italy
  • Matile, Stefan NCCR Chemical Biology, Department of Organic Chemistry, University of Geneva, 1211 Geneva, Switzerlan
  • Roux, Aurélien NCCR Chemical Biology, Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland
  • Vanni, Stefano Department of Biology, University of Fribourg, Fribourg, Switzerland
  • Weissman, Jonathan S. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA - Howard Hughes Medical Institute, San Francisco, CA 94158, USA
  • Riezman, Howard NCCR Chemical Biology, Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland -
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    05.10.2020
Published in:
  • Current Biology. - 2020, vol. 30, no. 19, p. 3775-3787.e7
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/309106
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