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11	Proteolytic Processing of Nlrp1b in the FIIND Domain is Required for Inflammasome Activity Frew, Bradley 21 March 2012 (has links) Nlrp1b is a NOD-like receptor of the innate immune system that upon sensing of anthrax lethal toxin oliogmerizes and forms a protein scaffold that binds to and activates pro-caspase-1; this complex is called an inflammasome. Nlrp1b is highly polymorphic and different alleles display an all or none ability to sense lethal toxin. Here I show that Nlrp1b is cleaved in the FIIND domain, and that the cleaved fragments remain associated even after activation by lethal toxin. The inflammasome activity of an inactive allele was restored by three mutations, one of which also restored cleavage. A heterologous cleavage site was inserted into an uncleaved mutant of Nlrp1b; induced proteolysis of the cleavage site rescued inflammasome activity. An uncleaved mutant of Nlrp1b showed no deficiency in FIIND self-association, but did have reduced recruitment of pro-caspase-1. These data provide evidence that cleavage of Nlrp1b is required for proper recruitment and activation of caspase-1. Microbiology Immunology Nlrp1b Nalp1b Inflammasome Anthrax Lethal toxin pyroptosis caspase-1 NLR Nlrp1 IL-1 NOD CARD8 Cleaved Cleavage Proteolysis Innate immune Pattern recognition receptor Inflammation FIIND CARD 0410