Détails de la réservation
- Le : 15 January 2020
- De : 11 h 00
- à : 12 h 30
- Salle : Salle de conférence
Détails de l'évènement
Directeur de Recherche CNRS, INSERM U1197,
Hôpital Paul Brousse, Villejuif
"A cytosolic unfolded protein response controls the scaffolding and signaling of innate immune complexes"
Multiple cytosolic innate sensors form large signalosomes after activation, but this assembly needs to be tightly regulated to avoid accumulation of misfolded aggregates. We found that the eIF2α kinase heme-regulated inhibitor (HRI) controls NOD1 signalosome folding and activation through a process requiring eukaryotic initiation factor 2α (eIF2α), the transcription factor ATF4, and the heat shock protein HSPB8. The HRI/eIF2α signaling axis was also essential for signaling downstream of the innate immune mediators NOD2, MAVS, and TRIF but dispensable for pathways dependent on MyD88 or STING. Moreover, filament-forming α-synuclein activated HRI-dependent responses, which suggests that the HRI pathway may restrict toxic oligomer formation. We propose that HRI, eIF2α, and HSPB8 define a novel cytosolic unfolded protein response (cUPR) essential for optimal innate immune signaling by large molecular platforms, functionally homologous to the PERK/eIF2α/HSPA5 axis of the endoplasmic reticulum UPR.
Bref descriptif :
Damien Arnoult is investigating innate immunity. His interest focuses on cytosolic innate sensors and their relationship with mitochondria. His recent work has revealed a new linking sensing of unfolded proteins and innate immune receptors.
- Nom : Johan GARAUDE