新的研究发现,死亡在整个细胞内以触发波方式移动,并在长距离范围内散播死亡的生物化学信号。据研究结果披露,这一死亡信号传播迅速,达每分钟30微米。
(a和b)用细胞色素c注射未成熟卵细胞导致色素沉着的变化:从注射部位扩散到卵母细胞的相对侧。(c和d)自发死亡的卵细胞的表面波。
细胞凋亡是一种非令人担忧的细胞死亡形式,它对新细胞的生长及组织的维持都是至关重要的。当某个细胞觉得大限已至,一个自行毁灭的信号会播放出来,从而触发细胞凋亡蛋白酶的活化,该酶可彻底地将细胞裂解。
然而,这一过程是如何在整个细胞中传播的还不清楚。这种情况对巨大的细胞(如蛙类的卵)尤其如此),因为在蛙类卵中的长距离扩散过于缓慢。先前的研究显示,细胞凋亡可能通过细胞质以自生性触发波进行传播,从而能在不丧失速度或强度的情况下进行长距离传播。
Xianrui Chang和James Ferrell在小试管中的非洲爪蟾卵中提取的细胞物质内进行了细胞凋亡信号的传播,并用荧光探针来显现细胞凋亡信号在细胞质中的传播。Chang和Ferrell发现的证据表明,触发波所推进的细胞凋亡的传播距离大于1毫米,并以每分钟近30微米的恒速传播。
在非洲爪蟾体内的卵细胞中也观察到了类似的细胞凋亡传播速度,这一速度之快无法用通过扩散的简单传播来解释。
这些发现确认了触发波是生物化学信号传导的一种重要方法,它提示在许多不同类型的细胞中以及在其它的细胞内和细胞间沟通事例中可能也会有类似的触发波。
http://dx.doi.org//10.1126/science.aah4065SIGNAL TRANSDUCTION
Apoptosis propagates through the cytoplasm as trigger waves
Xianrui Cheng1 and James E. Ferrell Jr.1,2*
Apoptosis is an evolutionarily conserved form of programmed cell death critical for development and tissue homeostasis in animals. The apoptotic control network includes several positive feedback loops that may allow apoptosis to spread through the cytoplasm in self-regenerating trigger waves. We tested this possibility in cell-free Xenopus laevis egg extracts and observed apoptotic trigger waves with speeds of ~30 micrometers per minute. Fractionation and inhibitor studies implicated multiple feedback loops in generating the waves. Apoptotic oocytes and eggs exhibited surface waves with speeds of ~30 micrometers per minute, which were tightly correlated with caspase activation. Thus, apoptosis spreads through trigger waves in both extracts and intact cells. Our findings show how apoptosis can spread over large distances within a cell and emphasize the general importance of trigger waves in cell signaling.