The NLRP3 inflammasome senses a range of cellular disturbances, although no consensus exists regarding a common mechanism. Canonical NLRP3 activation is blocked by high extracellular K+, regardless of the activating signal. We report here that canonical NLRP3 activation leads to Ca2+ flux and increased calpain activity. Activated calpain releases a pool of Caspase-1 sequestered by the cytoskeleton to regulate NLRP3 activation. Using electrophysiological recording, we found that resting-state eukaryotic membrane potential (MP) is required for this calpain activity, and depolarization by high extracellular K+ or artificial hyperpolarization results in the inhibition of calpain. Therefore, the MP/Ca2+/calpain/Caspase-1 axis acts as an independent regulatory mechanism for NLRP3 activity. This finding provides mechanistic insight into high K+-mediated inhibition of NLRP3 activation, and it offers an alternative model of NLRP3 inflammasome activation that does not involve K+ efflux.
Pubmed ID: 30157429 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCTC clone 929 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets donkey anti-goat IgG-HRP
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets Mouse IL-1 beta / IL-1F2
View all literature mentionsThis polyclonal targets PYCARD
View all literature mentionsThis polyclonal targets CASP1
View all literature mentionsThis monoclonal targets FLII
View all literature mentionsThis polyclonal targets Myh9
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis unknown targets Calpain 2 Large Subunit
View all literature mentionsThis polyclonal targets CAPN9
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsVector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentions