@article{5ef57b72b45f40c4b6379eb0f3005adb,
title = "Vps13-like proteins provide phosphatidylethanolamine for GPI anchor synthesis in the ER",
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-Ku{\v c}inskas 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.",
keywords = "Cell metabolism, Metabolism",
author = "Alexandre Toulmay and Whittle, {Fawn B.} and Jerry Yang and Xiaofei Bai and Jessica Diarra and Subhrajit Banerjee and Levine, {Tim P.} and Andy Golden and Prinz, {William A.}",
note = "Funding Information: This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The authors declare no completing financial interests. Funding Information: We thank A. Ferguson for technical assistance, the Caenorhabditis Genetics Center (National Institutes of Health, Office of Research Infrastructure Programs, P40OD010440) for C. elegans strains, the Flow Cytometry Core of the National Heart, Lung, and Blood Institute and D. Masison (National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD) for reagents, J. Nunnari (University of California, Davis, Davis, CA) and O. Cohen-Fix (National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD) for plasmids, Y. Murakami and T. Kinoshita (Osaka University, Osaka, Japan) for cell lines and helpful advice, and T. Balla for reading the manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Publisher Copyright: {\textcopyright} 2022 Toulmay et al.",
year = "2022",
month = mar,
day = "7",
doi = "10.1083/jcb.202111095",
language = "English (US)",
volume = "221",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "3",
}