The cytotoxic lymphocyte protease, Granzyme B, targets the cytoskeleton and perturbs microtubule polymerization dynamics
The cytotoxic lymphocyte protease, Granzyme B, targets the cytoskeleton and perturbs microtubule polymerization dynamics
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DOI：
10.1074/jbc.m509361200
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发表时间：
2006-03-24
影响因子：
4.8
通讯作者：
Martin, SJ
中科院分区：
文献类型：
--
作者：
Adrain, C;Duriez, PJ;Martin, SJ
颗粒酶B是一种来源于细胞毒性T淋巴细胞（CTL）和自然杀伤细胞（NK）颗粒的丝氨酸蛋白酶，在协调CTL和NK靶细胞的凋亡中起重要作用。在这里，我们报道颗粒酶B通过切割和去除α -微管蛋白的酸性c端尾部来靶向细胞骨架。与此一致的是，颗粒酶B在体外显著提高了微管聚合的速率，很可能是通过去除微管蛋白C末端的自抑制结构域。此外，将颗粒酶B递送到HeLa靶细胞中，以不依赖于caspase的方式促进了微管网络的戏剧性重组。这些数据表明，颗粒酶B直接攻击细胞骨架的一个主要组成部分，这可能有助于在CTL/ nk介导的杀伤过程中靶细胞的失能。
Granzyme B, a serine protease derived from cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell granules, plays an important role in coordinating apoptosis of CTL and NK target cells. Here, we report that granzyme B targets the cytoskeleton by cleaving and removing the acidic C-terminal tail of alpha-tubulin. Consistent with this, Granzyme B markedly enhanced rates of microtubule polymerization in vitro, most likely by removal of an autoinhibitory domain within the tubulin C terminus. Moreover, delivery of Granzyme B into HeLa target cells promoted dramatic reorganization of the microtubule network in a caspase-independent manner. These data reveal that granzyme B directly attacks a major component of the cell cytoskeleton, which may contribute to the incapacitation of target cells during CTL/NK-mediated killing.