ESCRT公司
颗粒酶
穿孔素
细胞生物学
内体
细胞毒性T细胞
颗粒酶B
溶细胞素
细胞溶解
生物
颗粒酶A
癌细胞
CTL公司*
化学
细胞内
癌症
体外
生物化学
基因
毒力
遗传学
作者
Alex T. Ritter,Gleb Shtengel,Chengpei Xu,Aubrey V. Weigel,David P. Hoffman,Melanie Freeman,Nirmala Iyer,Nensi Alivodej,David Ackerman,Ilia Voskoboinik,Joseph A. Trapani,Harald F. Hess,Ira Mellman
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2022-04-22
卷期号:376 (6591): 377-382
被引量:48
标识
DOI:10.1126/science.abl3855
摘要
Cytotoxic T lymphocytes (CTLs) and natural killer cells kill virus-infected and tumor cells through the polarized release of perforin and granzymes. Perforin is a pore-forming toxin that creates a lesion in the plasma membrane of the target cell through which granzymes enter the cytosol and initiate apoptosis. Endosomal sorting complexes required for transport (ESCRT) proteins are involved in the repair of small membrane wounds. We found that ESCRT proteins were precisely recruited in target cells to sites of CTL engagement immediately after perforin release. Inhibition of ESCRT machinery in cancer-derived cells enhanced their susceptibility to CTL-mediated killing. Thus, repair of perforin pores by ESCRT machinery limits granzyme entry into the cytosol, potentially enabling target cells to resist cytolytic attack.
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