title: Glycan region of GPI anchored-protein is required for cytocidal oligomerization of an anticancer parasporin-2, Cry46Aa1 protein, from Bacillus thuringiensis strain A1547.
abstract: Parasporin-2 (PS2), alternatively named Cry46Aa1, an anticancer protein derived from Bacillus thuringiensis strain A1547, causes specific cell damage via PS2 oligomerization in the cell membrane. Although PS2 requires glycosylphosphatidylinositol (GPI)-anchored proteins for its cytocidal action, their precise role is unknown. Here, we report that the glycan of GPI induces PS2 oligomerization, which causes cell death. Cytotoxicity, cell-binding and oligomerization of the toxin were not observed in GPI-anchored protein-deficient Chinese hamster ovary cells. Expression and protease-treatment analyses showed that the actions of the toxin were dependent on the glycan core, not the polypeptide moiety, of GPI-anchored proteins. However, surface expression of some GPI-anchored proteins is observed in PS2-insensitive cells. These data suggest that GPI-anchored proteins do not determine the target specificity, but instead function as a kind of coreceptor, in the cytocidal action of PS2.
authors.affiliation: Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Yuich
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka, Osaka 565-0871, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ashida
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka, Osaka 565-0871, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka, Osaka 565-0871, Japan.
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan; Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan. Electronic address: kitada@bio.kyutech.ac.jp.
authors.forename: Sakae
authors.initials: S
authors.lastname: Kitada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001413:Bacillus thuringiensis / Q000378:metabolism; D015153:Blotting, Western; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D004731:Endotoxins / Q000378:metabolism* / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D047468:Immunoprecipitation; D016133:Polymerase Chain Reaction; D011134:Polysaccharides; D011485:Protein Binding
chemical_list: D000970:Antineoplastic Agents; D004731:Endotoxins; D058973:Folate Receptors, GPI-Anchored; D011134:Polysaccharides; C515506:parasporin-2, Bacillus thuringiensis
keywords: Cry protein; GPI-anchored protein; Oligomer; Parasporin; Receptor