Vps13-like proteins provide phosphatidylethanolamine for GPI anchor synthesis in the ER

Alexandre Toulmay, Fawn B. Whittle, Jerry Yang, Xiaofei Bai, Jessica Diarra, Subhrajit Banerjee, Tim P. Levine, Andy Golden, William A. Prinz

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Glycosylphosphatidylinositol (GPI) is a glycolipid membrane anchor found on surface proteins in all eukaryotes. It is synthesized in the ER membrane. Each GPI anchor requires three molecules of ethanolamine phosphate (P-Etn), which are derived from phosphatidylethanolamine (PE). We found that efficient GPI anchor synthesis in Saccharomyces cerevisiae requires Csf1; cells lacking Csf1 accumulate GPI precursors lacking P-Etn. Structure predictions suggest Csf1 is a tube-forming lipid transport protein like Vps13. Csf1 is found at contact sites between the ER and other organelles. It interacts with the ER protein Mcd4, an enzyme that adds P-Etn to nascent GPI anchors, suggesting Csf1 channels PE to Mcd4 in the ER at contact sites to support GPI anchor biosynthesis. CSF1 has orthologues in Caenorhabditis elegans (lpd-3) and humans (KIAA1109/ TWEEK); mutations in KIAA1109 cause the autosomal recessive neurodevelopmental disorder Alkuraya-Kučinskas syndrome. Knockout of lpd-3 and knockdown of KIAA1109 reduced GPI-anchored proteins on the surface of cells, suggesting Csf1 orthologues in human cells support GPI anchor biosynthesis.

Original languageEnglish (US)
Article numbere202111095
JournalJournal of Cell Biology
Volume221
Issue number3
DOIs
StatePublished - Mar 7 2022
Externally publishedYes

Keywords

  • Cell metabolism
  • Metabolism

ASJC Scopus subject areas

  • Cell Biology

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