Caspase-3-generated fragment of gelsolin: Effector of morphological change in apoptosis
Caspase-3-generated fragment of gelsolin: Effector of morphological change in apoptosis
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DOI：
10.1126/science.278.5336.294
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发表时间：
1997-10-10
期刊：
影响因子：
56.9
通讯作者：
Williams, LT
中科院分区：
文献类型：
--
作者：
Kothakota, S;Azuma, T;Williams, LT
caspase-3 （CPP32, apopain， YAMA）家族半胱氨酸蛋白酶被认为是哺乳动物细胞凋亡的关键介质，Gelsolin是caspase-3的底物，通过筛选小的互补DNA库的翻译产物对caspase-3切割的敏感性。Gelsolin在体内以caspase依赖的方式在Fas刺激的细胞中裂解。caspase切割的凝胶蛋白在体外以Ca2+不依赖的方式切断肌动蛋白丝，凝胶蛋白切割产物在多种细胞类型中的表达导致细胞聚集，脱离板，并发生核断裂。与野生型中性粒细胞相比，从缺乏凝胶的小鼠中分离出的中性粒细胞在凋亡诱导后出现水泡和DNA断裂的时间延迟。因此，裂解凝胶可能是细胞凋亡过程中形态学变化的一种生理效应。
The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells, Gelsolin was identified as a substrate for caspase-3 by screening the translation products of small complementary DNA pools for sensitivity to cleavage by caspase-3. Gelsolin was cleaved in vivo in a caspase-dependent manner in cells stimulated by Fas. Caspase-cleaved gelsolin severed actin filaments in vitro in a Ca2+-independent manner, Expression of the gelsolin cleavage product in multiple cell types caused the cells to round up, detach from the plate, and undergo nuclear fragmentation. Neutrophils isolated from mice lacking gelsolin had delayed onset of both blebbing and DNA fragmentation, following apoptosis induction, compared with wild-type neutrophils. Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis.