title: Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling.
abstract: Glycosylphosphatidylinositols (GPIs) act as membrane anchors of many eukaryotic cell surface proteins. GPIs in various organisms have a common backbone consisting of ethanolamine phosphate (EtNP), three mannoses (Mans), one non-N-acetylated glucosamine, and inositol phospholipid, whose structure is EtNP-6Manα-2Manα-6Manα-4GlNα-6myoinositol-P-lipid. The lipid part is either phosphatidylinositol of diacyl or 1-alkyl-2-acyl form, or inositol phosphoceramide. GPIs are attached to proteins via an amide bond between the C-terminal carboxyl group and an amino group of EtNP. Fatty chains of inositol phospholipids are inserted into the outer leaflet of the plasma membrane. More than 150 different human proteins are GPI anchored, whose functions include enzymes, adhesion molecules, receptors, protease inhibitors, transcytotic transporters, and complement regulators. GPI modification imparts proteins with unique characteristics, such as association with membrane microdomains or rafts, transient homodimerization, release from the membrane by cleavage in the GPI moiety, and apical sorting in polarized cells. GPI anchoring is essential for mammalian embryogenesis, development, neurogenesis, fertilization, and immune system. Mutations in genes involved in remodeling of the GPI lipid moiety cause human diseases characterized by neurological abnormalities. Yeast Saccharomyces cerevisiae has >60 GPI-anchored proteins (GPI-APs). GPI is essential for growth of yeast. In this review, we discuss biosynthesis of GPI-APs in mammalian cells and yeast with emphasis on the lipid moiety.
authors.affiliation: WPI Immunology Frontier Research Center and Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan tkinoshi@biken.osaka-u.ac.jp.
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu 214122, China.
authors.forename: Morihisa
authors.initials: M
authors.lastname: Fujita
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis* / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism
chemical_list: D017261:Glycosylphosphatidylinositols; D008055:Lipids; D008565:Membrane Proteins
keywords: fatty acid remodeling; genetic disorder; glycosylphosphatidylinositol; peroxisome