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© Research
Event

Department of Microbiology : “How to design a kill switch: A lesson from the AIM2-ASC inflammasome”

Scientific Fields
Diseases
Organisms
Applications
Technique
Date
12
Jun 2018
Time
10:00:00
28 Rue du Docteur Roux, Paris, France
Address
Building: Centre François Jacob
Location
2018-06-12 10:00:00 2018-06-12 12:00:00 Europe/Paris Department of Microbiology : “How to design a kill switch: A lesson from the AIM2-ASC inflammasome” The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic double-stranded (ds)DNA, which signals various maladies such as pathogen invasion and genomic instability. We show here that longer dsDNA […] 28 Rue du Docteur Roux, Paris, France

About

The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic double-stranded (ds)DNA, which signals various maladies such as pathogen invasion and genomic instability. We show here that longer dsDNA is more effective in inducing AIM2 assembly, its self-propagation, and downstream ASC polymerization. This observation is related to the increased probability of forming the base of AIM2 filaments and indicates that the assembly discerns small dsDNA as noise at each signaling step. Filaments assembled by receptor AIM2, downstream ASC, and their joint complex all persist regardless of dsDNA, consequently generating sustained signal amplification and hysteresis. Furthermore, multiple positive feedback loops reinforce the assembly, as AIM2 and ASC filaments accelerate the assembly of nascent AIM2 with or without dsDNA. Together with a quantitative model of the assembly, our results indicate that an ultrasensitive digital circuit drives the assembly of the AIM2-ASC inflammasome.

Location

Building: Centre François Jacob
Address: 28 Rue du Docteur Roux, Paris, France