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

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NOD1 was one of the first NLR-family members shown to act as an important intracellular pattern-recognition molecule mediating antimicrobial activities in mammals. It has been demonstrated that perturbation of F-actin and RhoGTPase activity affects NOD1 and NOD2 signaling, however, the effectors of this process remained elusive. By using a multilayered high-throughput druggable genome wide siRNA screening approach to discover novel components specific for the NOD1 pathway, we identified the cofilin phosphatase SSH1, which acts downstream of RhoA-ROCK, as key regulator of NOD1 signaling. We show that SSH1 forms a complex with NOD1 at F-actin rich sites in human cells and is needed for NOD1-mediated responses towards TriDAP exposure and Shigella flexneri infection. Functionally this is achieved by SSH1-mediated activation of cofilin. Our findings reveal a previously unrecognized role for SSH1 in NOD1 signaling and provide a plausible unifying mechanistic explanation of how perturbations of the actin cytoskeleton can induce NOD1-mediated inflammatory responses.

Vyšlo v časopise: The Cofilin Phosphatase Slingshot Homolog 1 (SSH1) Links NOD1 Signaling to Actin Remodeling. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004351
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004351

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