Novel initiator caspase reporters uncover previously unknown features of caspase-activating cells
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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.
Baena-Lopez , L A , Arthurton , L , Bischoff , M , Vincent , J-P , Alexandre , C & McGregor , R 2018 , ' Novel initiator caspase reporters uncover previously unknown features of caspase-activating cells ' , Development , vol. 145 , no. 23 , dev170811 . https://doi.org/10.1242/dev.170811
Copyright © 2018 The Author(s). Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
DescriptionThis work was supported by Cancer Research UK (C49979/A17516) and the John Fell Fund, University of Oxford (162/001). L.A.B.-L. is a CRUK Career Development Fellow (C49979/A17516) and an Oriel College, University of Oxford, Hayward Fellow. L.A. is a PhD student supported by the Edward Penley Abraham Research Fund. M.B. is supported by Biotechnology and Biological Sciences Research Council (BB/M021084/1). J-P.V. and C.A. are supported by a European Research Council grant (WNTEXPORT; 294523) and the Medical Research Council (MRC U117584268).
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