The cofilin phosphatase slingshot homolog 1 (SSH1) links NOD1 signaling to actin remodeling.
PLoS Pathog
; 10(9): e1004351, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-25187968
ABSTRACT
NOD1 is an intracellular pathogen recognition receptor that contributes to anti-bacterial innate immune responses, adaptive immunity and tissue homeostasis. NOD1-induced signaling relies on actin remodeling, however, the details of the connection of NOD1 and the actin cytoskeleton remained elusive. Here, we identified in a druggable-genome wide siRNA screen the cofilin phosphatase SSH1 as a specific and essential component of the NOD1 pathway. We show that depletion of SSH1 impaired pathogen induced NOD1 signaling evident from diminished NF-κB activation and cytokine release. Chemical inhibition of actin polymerization using cytochalasin D rescued the loss of SSH1. We further demonstrate that NOD1 directly interacted with SSH1 at F-actin rich sites. Finally, we show that enhanced cofilin activity is intimately linked to NOD1 signaling. Our data thus provide evidence that NOD1 requires the SSH1/cofilin network for signaling and to detect bacterial induced changes in actin dynamics leading to NF-κB activation and innate immune responses.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Shigella flexneri
/
Actinas
/
Fosfoproteínas Fosfatases
/
Disenteria Bacilar
/
Cofilina 1
/
Proteína Adaptadora de Sinalização NOD1
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha