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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jiang-Yuan LiJian-Zhong Shao

Abstract

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 (DrNLRP1) from a zebrafish (D. rerio) model. This DrNLRP1 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 [DrCaspase]-A and DrCaspase-B) and maturation of D. rerio IL-1β in a D. rerio ASC (DrASC)-dependent manner. In this process, DrNLRP1 promotes the aggregation of DrASC into a filament with DrASCCARD core and DrASCPYD cluster. The assembly of DrNLRP1 inflammasome depends on the CARD-CARD homotypic interaction between DrNLRP1 and DrASCCARD core, and PYD-PYD interaction between DrCaspase-A/B and DrASCPYD cluster. The FIIND domain in DrNLRP1 is necessary for inflammasome assembly. To understand the mechanism of how the two DrCaspases are coordinated in DrNLRP1 inflammasome, we propose a two-step sequential activation model. In this model, the recruitment and activation of DrCaspase-A/B in the in...Continue Reading

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Citations

Mar 1, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhuang WangDahai Yang
Apr 15, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhi-Fei LiuJian-Zhong Shao
Sep 29, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wei ShiJian-Zhong Shao
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Nov 2, 2019·Fish & Shellfish Immunology·Shouwen ChenQin Liu
Jan 13, 2021·Cell Death & Disease·Zhihao XuTengchuan Jin
Mar 14, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Weijie ChenDahai Yang
May 1, 2021·International Journal of Molecular Sciences·Natsuki MorimotoJun-Ichi Hikima
Jul 13, 2021·Developmental and Comparative Immunology·Hao ChenDahai Yang
Nov 9, 2020·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Yongzhan MaiZini Lai

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