Titre
ASC filament formation serves as a signal amplification mechanism for inflammasomes.
Type
article
Institution
Externe
Périodique
Auteur(s)
Dick, M.S.
Auteure/Auteur
Sborgi, L.
Auteure/Auteur
Rühl, S.
Auteure/Auteur
Hiller, S.
Auteure/Auteur
Broz, P.
Auteure/Auteur
Liens vers les personnes
ISSN
2041-1723
Statut éditorial
Publié
Date de publication
2016
Volume
7
Première page
11929
Peer-reviewed
Oui
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.
PID Serval
serval:BIB_1F376E063F34
PMID
Open Access
Oui
Date de création
2017-10-25T09:05:19.016Z
Date de création dans IRIS
2025-05-20T19:40:04Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
ncomms11929.pdf
Version du manuscrit
published
Taille
1.73 MB
Format
Adobe PDF
PID Serval
serval:BIB_1F376E063F34.P001
Somme de contrôle
(MD5):196502e188a16a8ffc16b609bb4f23d9