Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis.
Members of the gasdermin (GSDM) family are pore-forming effectors that cause membrane permeabilization and pyroptosis, a lytic proinflammatory type of cell death. To reveal the functional evolution of GSDM-mediated pyroptosis at the transition from invertebrates to vertebrates, we conducted function...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-05-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002062 |
| _version_ | 1797830999954948096 |
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| author | Xinli Wang Xuxia Wei Yan Lu Qinghuan Wang Rong Fu Yin Wang Qin Wang Xiangyan Wang Shangwu Chen Anlong Xu Shaochun Yuan |
| author_facet | Xinli Wang Xuxia Wei Yan Lu Qinghuan Wang Rong Fu Yin Wang Qin Wang Xiangyan Wang Shangwu Chen Anlong Xu Shaochun Yuan |
| author_sort | Xinli Wang |
| collection | DOAJ |
| description | Members of the gasdermin (GSDM) family are pore-forming effectors that cause membrane permeabilization and pyroptosis, a lytic proinflammatory type of cell death. To reveal the functional evolution of GSDM-mediated pyroptosis at the transition from invertebrates to vertebrates, we conducted functional characterization of amphioxus GSDME (BbGSDME) and found that it can be cleaved by distinct caspase homologs, yielding the N253 and N304 termini with distinct functions. The N253 fragment binds to cell membrane, triggers pyroptosis, and inhibits bacterial growth, while the N304 performs negative regulation of N253-mediated cell death. Moreover, BbGSDME is associated with bacteria-induced tissue necrosis and transcriptionally regulated by BbIRF1/8 in amphioxus. Interestingly, several amino acids that are evolutionarily conserved were found to be important for the function of both BbGSDME and HsGSDME, shedding new lights on the functional regulation of GSDM-mediated inflammation. |
| first_indexed | 2024-04-09T13:45:07Z |
| format | Article |
| id | doaj.art-f21378df14724e43a5fc50b47bbdd7e7 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-09T13:45:07Z |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-f21378df14724e43a5fc50b47bbdd7e72023-05-09T05:30:44ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-05-01215e300206210.1371/journal.pbio.3002062Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis.Xinli WangXuxia WeiYan LuQinghuan WangRong FuYin WangQin WangXiangyan WangShangwu ChenAnlong XuShaochun YuanMembers of the gasdermin (GSDM) family are pore-forming effectors that cause membrane permeabilization and pyroptosis, a lytic proinflammatory type of cell death. To reveal the functional evolution of GSDM-mediated pyroptosis at the transition from invertebrates to vertebrates, we conducted functional characterization of amphioxus GSDME (BbGSDME) and found that it can be cleaved by distinct caspase homologs, yielding the N253 and N304 termini with distinct functions. The N253 fragment binds to cell membrane, triggers pyroptosis, and inhibits bacterial growth, while the N304 performs negative regulation of N253-mediated cell death. Moreover, BbGSDME is associated with bacteria-induced tissue necrosis and transcriptionally regulated by BbIRF1/8 in amphioxus. Interestingly, several amino acids that are evolutionarily conserved were found to be important for the function of both BbGSDME and HsGSDME, shedding new lights on the functional regulation of GSDM-mediated inflammation.https://doi.org/10.1371/journal.pbio.3002062 |
| spellingShingle | Xinli Wang Xuxia Wei Yan Lu Qinghuan Wang Rong Fu Yin Wang Qin Wang Xiangyan Wang Shangwu Chen Anlong Xu Shaochun Yuan Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis. PLoS Biology |
| title | Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis. |
| title_full | Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis. |
| title_fullStr | Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis. |
| title_full_unstemmed | Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis. |
| title_short | Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis. |
| title_sort | characterization of gsdme in amphioxus provides insights into the functional evolution of gsdm mediated pyroptosis |
| url | https://doi.org/10.1371/journal.pbio.3002062 |
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