Dismantling cell-cell contacts during apoptosis is coupled to a caspase-dependent proteolytic cleavage of beta-catenin.
Dismantling cell-cell contacts during apoptosis is coupled to a caspase-dependent proteolytic cleavage of beta-catenin.
复制标题
凋亡过程中拆卸细胞 - 细胞接触与β-catenin的caspase依赖性蛋白水解裂解耦合。
DOI：
10.1083/jcb.139.3.759
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发表时间：
1997-11-03
影响因子：
7.8
通讯作者：
Schneider, C
中科院分区：
文献类型：
--
作者：
Brancolini, C;Lazarevic, D;Rodriguez, J;Schneider, C
由细胞凋亡引起的细胞死亡是一个严格调控的过程，需要对细胞结构进行协调调整。半胱氨酸天冬氨酸蛋白酶家族已被证明在细胞凋亡中起关键作用。在这里，我们报告了在细胞凋亡过程中，肌动蛋白细胞骨架发生了特定和有序的变化。在此背景下，我们剖析了细胞死亡的第一个特征之一，即相邻细胞之间联系的切断。更具体地说，我们提供了在细胞-细胞黏附过程中有助于细胞骨架组织解体的机制。事实上，β-连环蛋白是一种已知的细胞间黏附调节因子，在诱导细胞凋亡后，在不同的细胞类型中被蛋白质降解。Caspase-3(cpp32/apopain/yama)在体外将β-catenin翻译成类似于在细胞凋亡中观察到的大小的形式。β-连环蛋白的切割，在体内的凋亡过程中和在体外处理Caspase-3后，去除了蛋白质的氨基和羧基末端区域。由此产生的β-连环蛋白产物不能与负责肌动蛋白细丝结合和组织的α-连环蛋白结合。这一证据表明，在细胞凋亡过程中，与细胞接触处的肌动蛋白细丝的连接可能会被拆除。我们的观察表明，caspase通过切割微丝系统的不同调节因子，协调细胞死亡过程中肌动蛋白细胞骨架发生的特定和连续的变化。
Cell death by apoptosis is a tightly regulated process that requires coordinated modification in cellular architecture. The caspase protease family has been shown to play a key role in apoptosis. Here we report that specific and ordered changes in the actin cytoskeleton take place during apoptosis. In this context, we have dissected one of the first hallmarks in cell death, represented by the severing of contacts among neighboring cells. More specifically, we provide demonstration for the mechanism that could contribute to the disassembly of cytoskeletal organization at cell–cell adhesion. In fact, β-catenin, a known regulator of cell–cell adhesion, is proteolytically processed in different cell types after induction of apoptosis. Caspase-3 (cpp32/apopain/yama) cleaves in vitro translated β-catenin into a form which is similar in size to that observed in cells undergoing apoptosis. β-Catenin cleavage, during apoptosis in vivo and after caspase-3 treatment in vitro, removes the amino- and carboxy-terminal regions of the protein. The resulting β-catenin product is unable to bind α-catenin that is responsible for actin filament binding and organization. This evidence indicates that connection with actin filaments organized at cell–cell contacts could be dismantled during apoptosis. Our observations suggest that caspases orchestrate the specific and sequential changes in the actin cytoskeleton occurring during cell death via cleavage of different regulators of the microfilament system.