RACK1 Mediates NLRP3 Inflammasome Activation by Promoting NLRP3 Active Conformation and Inflammasome Assembly
Copyright policy )RACK1 Mediates NLRP3 Inflammasome Activation by Promoting NLRP3 Active Conformation and Inflammasome Assembly
The NLRP3 inflammasome, a critical component of the innate immune system, induces caspase-1 activation and interleukin (IL)-1β maturation in response to microbial infection and cellular damage. However, aberrant activation of the NLRP3 inflammasome contributes to the pathogenesis of several inflammatory disorders, including cryopyrin-associated periodic syndromes, Alzheimer's disease, type 2 diabetes, and atherosclerosis. Here, we identify the receptor for activated protein C kinase 1 (RACK1) as a component of the NLRP3 complexes in macrophages. RACK1 interacts with NLRP3 and NEK7 but not ASC. Suppression of RACK1 expression abrogates caspase-1 activation and IL-1β release in response to NLRP3- but not NLRC4- or AIM2-activating stimuli. This RACK1 function is independent of its ribosomal binding activity. Mechanistically, RACK1 promotes the active conformation of NLRP3 induced by activating stimuli and subsequent inflammasome assembly. These results demonstrate that RACK1 is a critical mediator for NLRP3 inflammasome activation.
- University of Michigan–Ann Arbor United States
- WAYNE STATE UNIVERSITY
- Wayne State University United States
- Wayne State University School of Medicine United States
- Hospital Universitario Virgen de la Arrixaca Spain
Male, RACK1, QH301-705.5, Inflammasomes, Interleukin-1beta, Receptors for Activated C Kinase, Mice, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Humans, NIMA-Related Kinases, Biology (General), Macrophages, Caspase 1, NLRP3 inflammasome, CARD Signaling Adaptor Proteins, Mice, Inbred C57BL, HEK293 Cells, IL-1β, Caspase-1, Female, NEK7
Male, RACK1, QH301-705.5, Inflammasomes, Interleukin-1beta, Receptors for Activated C Kinase, Mice, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Humans, NIMA-Related Kinases, Biology (General), Macrophages, Caspase 1, NLRP3 inflammasome, CARD Signaling Adaptor Proteins, Mice, Inbred C57BL, HEK293 Cells, IL-1β, Caspase-1, Female, NEK7
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