Universität zu Köln

Bielig, Harald, Lautz, Katja, Braun, Peter R., Menning, Maureen, Machuy, Nikolaus, Bruegmann, Christine, Barisic, Sandra, Eisler, Stephan A., Andreel, Maria, Zurek, Birte, Kashkar, Hamid, Sansonetti, Philippe J., Hausser, Angelika, Meyer, Thomas F. ORCID: 0000-0002-6120-8679 and Kufer, Thomas A. (2014). The Cofilin Phosphatase Slingshot Homolog 1 (SSH1) Links NOD1 Signaling to Actin Remodeling. PLoS Pathog., 10 (9). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7374

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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-kappa B 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-kappa B activation and innate immune responses.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bielig, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Lautz, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Peter R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Menning, Maureen UNSPECIFIED UNSPECIFIED UNSPECIFIED Machuy, Nikolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruegmann, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Barisic, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Eisler, Stephan A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andreel, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Zurek, Birte UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED Sansonetti, Philippe J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hausser, Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Thomas F. UNSPECIFIED orcid.org/0000-0002-6120-8679 UNSPECIFIED Kufer, Thomas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-431426
DOI:	10.1371/journal.ppat.1004351
Journal or Publication Title:	PLoS Pathog.
Volume:	10
Number:	9
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7374
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; TOLL-LIKE RECEPTOR; INNATE IMMUNITY; BACTERIAL PEPTIDOGLYCAN; INFLAMMATORY RESPONSES; MYELOMONOCYTIC CELLS; DEPENDENT PATHWAY; PROTEIN-KINASE; RNAI SCREENS; ACTIVATION Multiple languages Microbiology; Parasitology; Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43142