Open AccessThe Cofilin Phosphatase Slingshot Homolog 1 (SSH1) Links NOD1 Signaling to Actin Remodeling
Author(s) -
Harald Bielig,
Katja Lautz,
Peter Braun,
Maureen Menning,
Nikolaus Machuy,
Christine Brügmann,
Sandra Barišić,
Stephan A. Eisler,
Maria Andree,
Birte Zurek,
Hamid Kashkar,
Philippe Sansonetti,
Angelika Haußer,
Thomas F. Meyer,
Thomas A. Kufer
Publication year - 2014
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1004351
Subject(s) - cofilin , actin remodeling , microbiology and biotechnology , biology , cytochalasin d , actin cytoskeleton , actin , nod1 , innate immune system , signal transduction , cytoskeleton , immunology , immune system , biochemistry , cell , nod2
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.