ASC filament formation serves as a signal amplification mechanism for inflammasomes.

Détails

Ressource 1Télécharger: ncomms11929.pdf (1768.73 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_1F376E063F34
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
ASC filament formation serves as a signal amplification mechanism for inflammasomes.
Périodique
Nature Communications
Auteur(s)
Dick M.S., Sborgi L., Rühl S., Hiller S., Broz P.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
7
Pages
11929
Langue
anglais
Résumé
A hallmark of inflammasome activation is the ASC speck, a micrometre-sized structure formed by the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which consists of a pyrin domain (PYD) and a caspase recruitment domain (CARD). Here we show that assembly of the ASC speck involves oligomerization of ASC(PYD) into filaments and cross-linking of these filaments by ASC(CARD). ASC mutants with a non-functional CARD only assemble filaments but not specks, and moreover disrupt endogenous specks in primary macrophages. Systematic site-directed mutagenesis of ASC(PYD) is used to identify oligomerization-deficient ASC mutants and demonstrate that ASC speck formation is required for efficient processing of IL-1β, but dispensable for gasdermin-D cleavage and pyroptosis induction. Our results suggest that the oligomerization of ASC creates a multitude of potential caspase-1 activation sites, thus serving as a signal amplification mechanism for inflammasome-mediated cytokine production.

Pubmed
Web of science
Open Access
Oui
Création de la notice
25/10/2017 11:05
Dernière modification de la notice
20/08/2019 13:55
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