The Cofilin Phosphatase Slingshot Homolog 1 (SSH1) Links NOD1 Signaling to Actin Remodeling

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. © 2014 bielig et al.