Universität zu Köln

Kuri, Paola ORCID: 0000-0003-4219-8417, Schieber, Nicole L. ORCID: 0000-0002-3212-5057, Thumberger, Thomas ORCID: 0000-0001-8485-457X, Wittbrodt, Joachim ORCID: 0000-0001-8550-7377, Schwab, Yannick ORCID: 0000-0001-8027-1836 and Leptin, Maria ORCID: 0000-0001-7097-348X (2017). Dynamics of in vivo ASC speck formation. J. Cell Biol., 216 (9). S. 2891 - 2910. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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Abstract

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 CRI SPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong ASC expression in the skin and other epithelia that act as barriers to insult. A toxic stimulus triggered speck formation and rapid pyroptosis in keratinocytes in vivo. Macrophages engulfed and digested that speck-containing, pyroptotic debris. A three-dimensional, ultrastructural reconstruction, based on correlative light and electron microscopy of the in vivo assembled specks revealed a compact network of highly intercrossed filaments, whereas pyrin domain (PYD) or caspase activation and recruitment domain alone formed filamentous aggregates. The effector caspase is recruited through PYD, whose overexpression induced pyroptosis but only after substantial delay. Therefore, formation of a single, compact speck and rapid cell-death induction in vivo requires a full-length ASC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kuri, Paola UNSPECIFIED orcid.org/0000-0003-4219-8417 UNSPECIFIED Schieber, Nicole L. UNSPECIFIED orcid.org/0000-0002-3212-5057 UNSPECIFIED Thumberger, Thomas UNSPECIFIED orcid.org/0000-0001-8485-457X UNSPECIFIED Wittbrodt, Joachim UNSPECIFIED orcid.org/0000-0001-8550-7377 UNSPECIFIED Schwab, Yannick UNSPECIFIED orcid.org/0000-0001-8027-1836 UNSPECIFIED Leptin, Maria UNSPECIFIED orcid.org/0000-0001-7097-348X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-220169
DOI:	10.1083/jcb.201703103
Journal or Publication Title:	J. Cell Biol.
Volume:	216
Number:	9
Page Range:	S. 2891 - 2910
Date:	2017
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INFLAMMASOME ADAPTER ASC; CELL-DEATH; NLRP3 INFLAMMASOME; ZEBRAFISH; ACTIVATION; SKIN; INTERLEUKIN-1-BETA; PHOSPHORYLATION; EXPRESSION; MECHANISM Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22016