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.
Vps13-like proteins provide phosphatidylethanolamine for GPI anchor synthesis in the ER
- Views Icon Views
- Share Icon Share
- Search Site
Alexandre Toulmay, Fawn B. Whittle, Jerry Yang, Xiaofei Bai, Jessica Diarra, Subhrajit Banerjee, Tim P. Levine, Andy Golden, William A. Prinz; Vps13-like proteins provide phosphatidylethanolamine for GPI anchor synthesis in the ER. J Cell Biol 7 March 2022; 221 (3): e202111095. doi: https://doi.org/10.1083/jcb.202111095
Download citation file: