穿孔素
颗粒酶
内体
细胞生物学
胞浆
内吞作用
化学
颗粒酶B
细胞膜
生物
细胞
胞吐
膜
细胞内
生物化学
细胞毒性T细胞
酶
体外
作者
Jérôme Thiery,Dennis Keefe,Steeve Boulant,Emmanuel Boucrot,Michael Walch,Denis Martinvalet,Ing Swie Goping,R. Chris Bleackley,Tomas Kirchhausen,Judy Lieberman
摘要
How the pore-forming protein perforin delivers apoptosis-inducing granzymes to the cytosol of target cells is uncertain. Perforin induces a transient Ca2+ flux in the target cell, which triggers a process to repair the damaged cell membrane. As a consequence, both perforin and granzymes are endocytosed into enlarged endosomes called 'gigantosomes'. Here we show that perforin formed pores in the gigantosome membrane, allowing endosomal cargo, including granzymes, to be gradually released. After about 15 min, gigantosomes ruptured, releasing their remaining content. Thus, perforin delivers granzymes by a two-step process that involves first transient pores in the cell membrane that trigger the endocytosis of granzyme and perforin and then pore formation in endosomes to trigger cytosolic release.
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