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

PLoS Pathogens

Christine Brügmann¹  Peter R. Braun¹  Thomas F. Meyer²  Nikolaus Machuy³  Hamid Kashkar³  Harald Bielig³  Birte Zurek³  Philippe J. Sansonetti³  Sandra Barisic³  Katja Lautz³  Maria Andree⁴  Stephan A. Eisler⁴  Thomas A. Kufer⁵  Maureen Menning⁶  Angelika Hausser⁷ 

[1] Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany;INSERM U786, Institut Pasteur, Paris, France;Institute for Medical Microbiology, Immunology and Hygiene, Cologne, Germany;Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany;Microbiologie et Maladies Infectieuses, Collège de France, Paris, France;Steinbeis-Innovationszentrum Center for Systems Biomedicine, Falkensee, Germany;Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France

关键词: Small interfering RNAs;    Transcription factors;    Actins;    Enzyme-linked immunoassays;    Shigella flexneri;    Immune receptor signaling;    Phosphatases;    Secretion;   

DOI  :  10.1371/journal.ppat.1004351

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY