Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis

Li, Hanqing; Wang, Xin; Yu, Lanjie; Wang, Junwei; Cao, Yanghui; Ma, Bo; Zhang, Wenlong

doi:10.3389/fimmu.2022.1078526

“…No additional gasdermins are found in amphibians or birds, therefore, these clades encode GSDME, PJVK, and GSDMA. Among these, GSDME is activated by caspase-3 to execute pyroptosis (Li et al, 2022 ). Our and other molecular phylogeny analysis identified 3 amphibians in the caecilian order with GSDMA genes (Yuan et al, 2022 ;Wang et al, 2023b).…”

Section: Phylogenetic Analysis Of Gsdm Proteinsmentioning

confidence: 49%

Caspase-1 activates gasdermin A in non-mammals

Billman,

Kovacs,

Wei

et al. 2024

Preprint

0

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Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles and birds gave rise to GSDMA-D in mammals. Uniquely in our tree, amphibian, reptile and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals. We demonstrate that amphibians, reptiles and birds engage pyroptosis using caspase-1 and GSDMA, filling an evolutionary gap in which caspase-1 cleaves GSDME in fish and GSDMD in mammals.

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“…No additional gasdermins are found in amphibians or birds, therefore, these clades encode GSDME, PJVK, and GSDMA. Among these, GSDME is activated by caspase-3 to execute pyroptosis (Li et al, 2022 ). Our and other molecular phylogeny analysis identified 3 amphibians in the caecilian order with GSDMA genes (Yuan et al, 2022 ;Wang et al, 2023 b).…”

Section: Phylogenetic Analysis Of Gsdm Proteinsmentioning

confidence: 51%

Caspase-1 activates gasdermin A in all non-mammals

Billman,

Kovacs,

Wei

et al. 2023

Preprint

1

0

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Gasdermins oligomerize to form pores in the cell membrane, causing programmed lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family and focus on the first gene amplification event that gave rise to mammal GSDMA-D by studying GSDMA in non-mammal species including amphibians, reptiles, and birds. Remarkably, GSDMA in numerous bird species contains the canonical caspase-1 cleavage site YVAD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals. We demonstrate that amphibians, reptiles and birds engage pyroptosis using caspase-1 and GS-DMA, filling an evolutionary gap in which caspase-1 cleaves GSDME in fish and GSDMD in mammals.

show abstract

“…No additional gasdermins are found in amphibians or birds, therefore, these clades encode GSDME , PJVK , and GSDMA . Among these, GSDME is activated by caspase-3 to execute pyroptosis ( Li et al, 2022 ). Our and other molecular phylogeny analysis identified three amphibians in the caecilian order with GSDMA genes ( Yuan et al, 2022 ; Wang et al, 2023b ).…”

Section: Resultsmentioning

confidence: 99%

Caspase-1 activates gasdermin A in non-mammals

Billman,

Kovacs,

Wei

et al. 2024

eLife

View full text Add to dashboard Cite

Gasdermins oligomerize to form pores in the cell membrane, causing programmed lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family and focus on the first gene amplification event that gave rise to mammal GSDMA-D by studying GSDMA in non-mammal species including amphibians, reptiles, and birds. Remarkably, GSDMA in numerous bird species contains the canonical caspase-1 cleavage site YVAD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals. We demonstrate that amphibians, reptiles and birds engage pyroptosis using caspase-1 and GS-DMA, filling an evolutionary gap in which caspase-1 cleaves GSDME in fish and GSDMD in mammals.

show abstract

Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis

Cited by 11 publications

References 32 publications

Caspase-1 activates gasdermin A in non-mammals

Caspase-1 activates gasdermin A in non-mammals

Caspase-1 activates gasdermin A in all non-mammals

Caspase-1 activates gasdermin A in non-mammals

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