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Vol. 14, Issue 10, 4285-4295, October 2003
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* Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan;
The Second Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan; and
Department of Blood Transfusion Medicine and Hematology, Wakayama Medical University, Wakayama 641-8510, Japan
Submitted March 31, 2003;
Revised May 28, 2003;
Accepted May 28, 2003
Monitoring Editor: Reid Gilmore
Many cell surface proteins are anchored to a membrane via a glycosylphosphatidylinositol (GPI), which is attached to the C termini in the endoplasmic reticulum. The inositol ring of phosphatidylinositol is acylated during biosynthesis of GPI. In mammalian cells, the acyl chain is added to glucosaminyl phosphatidylinositol at the third step in the GPI biosynthetic pathway and then is usually removed soon after the attachment of GPIs to proteins. The mechanisms and roles of the inositol acylation and deacylation have not been well clarified. Herein, we report derivation of human and Chinese hamster mutant cells defective in inositol acylation and the gene responsible, PIG-W. The surface expressions of GPI-anchored proteins on these mutant cells were greatly diminished, indicating the critical role of inositol acylation. PIG-W encodes a 504-amino acid protein expressed in the endoplasmic reticulum. PIG-W is most likely inositol acyltransferase itself because the tagged PIG-W affinity purified from transfected human cells had inositol acyltransferase activity and because both mutant cells were complemented with PIG-W homologs of Saccharomyces cerevisiae and Schizosaccharomyces pombe. The inositol acylation is not essential for the subsequent mannosylation, indicating that glucosaminyl phosphatidylinositol can flip from the cytoplasmic side to the luminal side of the endoplasmic reticulum.
These authors contributed equally to this work.
Abbreviations used: DAF, decay accelerating factor; GlcN, glucosamine; GlcNAc, N-acetylglucosamine; GlcN-PI(C8), glucosamine-PI bearing dioctanoyl-PI; GPI, glycosylphosphatidylinositol; GPI-PLD, glycosylphosphatidylinositol-specific phospholipase D; MT1, first mannosyltransferase; P-EtN, phosphoethanolamine; PI, phosphatidylinositol; PI-PLC, phosphatidylinositol-specific phospholipase C.
Note added to proof. Two articles describing PIG-W homologue of Saccharomyces cerevisiae have appeared recently: Tsukahara, K., Hata, K., Nakamoto, K., Sagane, K., Watanabe, N., Kuromitsu, J., Kai, J., Tsuchiya, M., Ohba, F., Jigami, Y., Yoshimatsu, K., and Nagasu, T. (2003) Medical genetics approach towards identifying the molecular target of a navel inhibitor of fungal cell wall assembly. Mol. Microbiol. 48, 1029–1042; Umemura, M., Okamoto, M., Nakayama, K., Sagane, K., Tsukahara, K., Hata, K., and Jigami, Y. (2003) GWT1 gene is required for inositol acylation of glycosylphosphatidylinositol anchors in yeast. J. Biol. Chem. 278, 23639–23647.
Corresponding author. E-mail address: tkinoshi{at}biken.osakau.ac.jp.
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