Cytotoxic cell granule-mediated apoptosis: Perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation
Cytotoxic cell granule-mediated apoptosis: Perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation
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DOI：
10.1016/s1074-7613(02)00286-8
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发表时间：
2002-03-01
期刊：
影响因子：
32.4
通讯作者：
Froelich, CJ
中科院分区：
文献类型：
--
作者：
Metkar, SS;Wang, BK;Froelich, CJ
细胞毒性细胞颗粒介导的死亡过程中凋亡颗粒酶的穿孔素（PFN）依赖性传递的机制仍然是推测性的。颗粒酶B。(GrB)和穿孔素与蛋白聚糖丝甘肽（SG）以多聚体复合物的形式共存于细胞毒性颗粒中，细胞毒性细胞仅分泌大分子GrB-SG。与PFN作为颗粒酶通过质膜的通道的观点相反，单体PFN和引人注目的PFN-SG复合物显示出介导大分子GrB-SG的胞质递送而不产生可检测的质膜孔。这些结果表明，颗粒介导的细胞凋亡的现象，即靶细胞感知颗粒内容物作为一个多聚体复合物组成的SG，PFN，和颗粒酶，这是，分别是支架，转运，和靶向/信息组件的模块化交付系统。
The mechanism underlying perforin (PFN)-dependent delivery of apoptotic granzymes during cytotoxic cell granule-mediated death remains speculative. Granzyme B. (GrB) and perforin were found to coexist as multimeric complexes with the proteoglycan serglycin (SG) in cytotoxic granules, and cytotoxic cells were observed to secrete exclusively macromolecular GrB-SG. Contrary to the view that PFN acts as a gateway for granzymes through the plasma membrane, monomeric PFN and, strikingly, PFN-SG complexes were shown to mediate cytosolic delivery of macromolecular GrB-SG without producing detectable plasma membrane pores. These results indicate that granule-mediated apoptosis represents a phenomenon whereby the target cell perceives granule contents as a multimeric complex consisting of SG, PFN, and granzymes, which are, respectively, the scaffold, translocator, and targeting/informational components of this modular delivery system.