Gasdermin E permits interleukin-1 beta release in distinct sublytic and pyroptotic phases.
Gasdermin E permits interleukin-1 beta release in distinct sublytic and pyroptotic phases.
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Gasdermin E允许白细胞介素-1 β在不同的亚裂解和热解阶段释放。
DOI：
10.1016/j.celrep.2021.108998
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发表时间：
2021-04-13
期刊：
影响因子：
8.8
通讯作者：
Abbott DW
中科院分区：
文献类型：
--
作者：
Zhou B;Abbott DW
细胞炎性小体激活导致孔形成蛋白gasdermin D（GSDMD）的半胱天冬酶-1切割，随后引起细胞死亡和细胞因子释放。在这里，我们澄清了相关的家庭成员gasdermin E（GSDME）在这个过程中的模糊作用。GSDMD缺陷细胞中的炎性体刺激导致GSDME的凋亡半胱天冬酶裂解。内源性GSDME激活允许亚溶解性、连续的白细胞介素-1 β（IL-1β）释放和膜渗漏，即使在GSDMD充足的细胞中，而异位表达导致GSDME寡聚化的焦亡和IL-1β的完全释放，类似于GSDMD焦亡。我们发现，NLRP 3和NLRP 1炎性小体最终同时依赖于两种gasdermin进行IL-1β加工，并分别从其诱导细胞裂解的能力中释放。因此，我们的研究确定GSDME作为IL-1β释放的管道，而不依赖于其导致细胞死亡的能力。Gasdermin D是细胞炎性小体激活后的焦亡的直接效应物。Zhou和Abbott证明，同源gasdermin E在不依赖于细胞裂解的亚裂解期中继发于IL-1β的释放而被激活，这需要更高的gasdermin E存在和大量的孔形成。
Cellular inflammasome activation causes caspase-1 cleavage of the pore-forming protein gasdermin D (GSDMD) with subsequent pyroptotic cell death and cytokine release. Here, we clarify the ambiguous role of the related family member gasdermin E (GSDME) in this process. Inflammasome stimulation in GSDMD-deficient cells led to apoptotic caspase cleavage of GSDME. Endogenous GSDME activation permitted sublytic, continuous interleukin-1β (IL-1β) release and membrane leakage, even in GSDMD-sufficient cells, whereas ectopic expression led to pyroptosis with GSDME oligomerization and complete liberation of IL-1β akin to GSDMD pyroptosis. We find that NLRP3 and NLRP1 inflammasomes ultimately rely concurrently on both gasdermins for IL-1β processing and release separately from their ability to induce cell lysis. Our study thus identifies GSDME as a conduit for IL-1β release independent of its ability to cause cell death. Gasdermin D is the immediate effector of pyroptosis after cellular inflammasome activation. Zhou and Abbott demonstrate that the homologous gasdermin E is activated secondarily to release of IL-1β in a sublytic phase that is independent of cell lysis, which requires higher gasdermin E presence and substantial pore formation.
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形成孔的蛋白质加油D可以调节白细胞介素-1的巨噬细胞分泌。
影响因子：
32.4
作者：
Evavold CL;Ruan J;Tan Y;Xia S;Wu H;Kagan JC
通讯作者：
Kagan JC
影响因子：
4.8
作者：
Chirieleison, Steven M.;Marsh, Rebecca A.;Abbott, Derek W.
通讯作者：
Abbott, Derek W.
DOI：
10.1073/pnas.1607769113
发表时间：
2016-07-12
影响因子：
11.1
作者：
Aglietti, Robin A.;Estevez, Alberto;Dueber, Erin C.
通讯作者：
Dueber, Erin C.
DOI：
10.1126/science.1240988
发表时间：
2013-09-13
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
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