Dynamics of ASC speck formation during skin inflammatory responses in vivo
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چکیده
17 Activated danger or pathogen sensors trigger assembly of the inflammasome adaptor ASC into 18 specks, large signalling platforms considered hallmarks of inflammasome activation. Because a 19 lack of in vivo tools has prevented the study of endogenous ASC dynamics, we generated a live 20 ASC reporter through CRISPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong 21 ASC expression in the skin and other epithelia that act as barriers to insult. A toxic stimulus 22 triggered speck formation and rapid pyroptosis in keratinocytes in vivo. Macrophages engulfed 23 and digested this speck-containing pyroptotic debris. A 3D ultrastructural reconstruction based on 24 CLEM of in vivo assembled specks revealed a compact network of highly intercrossed filaments, 25 whereas PYD or CARD alone formed filamentous aggregates. The effector caspase is recruited 26 through PYD, whose overexpression induced pyroptosis, but after substantial delay. Therefore, 27 formation of a single compact speck and rapid cell death induction in vivo requires full-length 28 ASC. 29 . CC-BY-NC-ND 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/111542 doi: bioRxiv preprint first posted online Feb. 27, 2017;
منابع مشابه
Dynamics of in vivo ASC speck formation
Activated danger or pathogen sensors trigger assembly of the inflammasome adaptor ASC into specks, large signaling platforms considered hallmarks of inflammasome activation. Because a lack of in vivo tools has prevented the study of endogenous ASC dynamics, we generated a live ASC reporter through CRISPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong ASC expression in the skin ...
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تاریخ انتشار 2017