English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

NLRP1 inflammasome is one of the best-characterized inflammasomes in humans and other mammals. However, the existence of this inflammasome in nonmammalian species remains poorly understood. In this study, we report the molecular and functional identification of an NLRP1 homolog, Danio rerio NLRP1 ( Dr NLRP1) from a zebrafish ( D. rerio ) model. This Dr NLRP1 possesses similar structural architecture to mammalian NLRP1s. It can trigger the formation of a classical inflammasome for the activation of zebrafish inflammatory caspases ( D. rerio Caspase [ Dr Caspase]-A and Dr Caspase-B) and maturation of D. rerio IL-1β in a D. rerio ASC ( Dr ASC)-dependent manner. In this process, Dr NLRP1 promotes the aggregation of Dr ASC into a filament with Dr ASC CARD core and Dr ASC PYD cluster. The assembly of Dr NLRP1 inflammasome depends on the CARD-CARD homotypic interaction between Dr NLRP1 and Dr ASC CARD core, and PYD-PYD interaction between Dr Caspase-A/B and Dr ASC PYD cluster. The FIIND domain in Dr NLRP1 is necessary for inflammasome assembly. To understand the mechanism of how the two Dr Caspases are coordinated in Dr NLRP1 inflammasome, we propose a two-step sequential activation model. In this model, the recruitment and activation of Dr Caspase-A/B in the inflammasome is shown in an alternate manner, with a preference for Dr Caspase-A followed by a subsequent selection for Dr Caspase-B. By using morpholino oligonucleotide-based knockdown assays, the Dr NLRP1 inflammasome was verified to play important functional roles in antibacterial innate immunity in vivo. These observations demonstrate that the NLRP1 inflammasome originated as early as in teleost fish. This finding not only gives insights into the evolutionary history of inflammasomes but also provides a favorable animal model for the study of NLRP1 inflammasome-mediated immunology and diseases.

the journal of immunology/the journal of immunology

Characterization of an NLRP1 Inflammasome from Zebrafish Reveals a Unique Sequential Activation Mechanism Underlying Inflammatory Caspases in Ancient Vertebrates