Kitada Sakae, Abe Yuichi, Maeda Toshitaka, Shimada Hiroyasu
Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 812-8581, Japan.
Toxicology. 2009 Oct 1;264(1-2):80-8. doi: 10.1016/j.tox.2009.07.016. Epub 2009 Jul 29.
Parasporin-2 (PS2) is a Bacillus thuringiensis inclusion protein that reacts intensively with human hepatoma cells. This antitumour toxin oligomerizes at the cell surface via binding to lipid rafts, leading to the cell lysis with typical blebs around peripheral cells. We find here that glycosylphosphatidylinositol (GPI)-anchored proteins are involved in the cytocidal actions. Depletion of the cellular cholesterol and loss of sphingolipid in lipid rafts slightly decreased cytolysis by PS2. Beyond those, the cells temporally resisted PS2 with reduction of the toxin binding after GPI-anchored proteins were cleaved off by phosphatidylinositol-specific phospholipase C. PS2 and aerolysin showed individual cytocidal specificity while aerolysin's receptor is GPI-anchored proteins. When we confirmed expression of GPI-anchored proteins on four cell lines, showing different cytotoxicity by PS2, GPI-anchored proteins were evenly expressed on the cells. Therefore, PS2 requires a kind of GPI-anchored proteins for the effective cytolysis.
副芽孢蛋白-2（PS2）是一种苏云金芽孢杆菌内含蛋白，能与人类肝癌细胞发生强烈反应。这种抗肿瘤毒素通过与脂筏结合在细胞表面形成寡聚体，导致细胞裂解，并在外周细胞周围形成典型的泡状突起。我们在此发现，糖基磷脂酰肌醇（GPI）锚定蛋白参与了细胞杀伤作用。细胞胆固醇的消耗和脂筏中鞘脂的丢失会使PS2引起的细胞溶解略有减少。除此之外，在用磷脂酰肌醇特异性磷脂酶C切除GPI锚定蛋白后，细胞会暂时抵抗PS2，毒素结合减少。PS2和气溶素表现出各自的细胞杀伤特异性，而气溶素的受体是GPI锚定蛋白。当我们在四种对PS2表现出不同细胞毒性的细胞系上证实了GPI锚定蛋白的表达时，GPI锚定蛋白在这些细胞上均匀表达。因此，PS2有效细胞溶解需要一种GPI锚定蛋白。
