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Novel initiator caspase reporters uncover previously unknown features of caspase-activating cells

机译:新型引发剂胱天蛋酶记者发现胱天蛋白激活细胞的先前未知特征

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摘要

The caspase-mediated regulation of many cellular processes, including apoptosis, justifies the substantial interest in understanding all of the biological features of these enzymes. To complement functional assays, it is crucial to identify caspase-activating cells in live tissues. Our work describes novel initiator caspase reporters that, for the first time, provide direct information concerning the initial steps of the caspase activation cascade in Drosophila tissues. One of our caspase sensors capitalises on the rapid subcellular localisation change of a fluorescent marker to uncover novel cellular apoptotic events relating to the actin-mediated positioning of the nucleus before cell delamination. The other construct benefits from caspase-induced nuclear translocation of a QF transcription factor. This feature enables the genetic manipulation of caspase-activating cells and reveals the spatiotemporal patterns of initiator caspase activity. Collectively, our sensors offer experimental opportunities not available by using previous reporters and have proven useful to illuminate previously unknown aspects of caspase-dependent processes in apoptotic and non-apoptotic cellular scenarios.
机译:Caspase介导的许多细胞过程的调节,包括细胞凋亡,证明了了解这些酶的所有生物学特征的实质性兴趣。为了补充功能测定,鉴定活组织中的胱天蛋白激活细胞至关重要。我们的作品描述了新的引发剂胱天蛋酶记者,这是第一次提供关于果蝇组织中胱天蛋白酶激活级联的初始步骤的直接信息。我们的一个Caspase传感器大写荧光标记的快速亚细胞定位变化,以发现与细胞分层前核的肌动蛋白介导的肌动蛋白介导的定位有关的新细胞凋亡事件。其他构建与QF转录因子的核易位核易位的影响。该特征能够实现胱天蛋白激活细胞的遗传操作,并揭示起始剂胱天蛋白酶活性的时空模式。统称,我们的传感器提供了使用以前的记者无法使用的实验机会,并证明在凋亡和非凋亡细胞场景中阐明了患者依赖性过程的先前未知的方面。

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