The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.
Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway
Open accessAbstract
Summary The process of pyroptosis is mediated by inflammasomes and a downstream effector known as gasdermin D (GSDMD). Upon cleavage by inflammasome-associated caspases, the N-terminal domain of GSDMD forms membrane pores that promote cytolysis. Numerous proteins promote GSDMD cleavage, but none are known to be required for pore formation after GSDMD cleavage. Herein, we report a forward genetic screen that identified the Ragulator-Rag complex as being necessary for GSDMD pore formation and pyroptosis in macrophages. Mechanistic analysis revealed that Ragulator-Rag is not required for GSDMD cleavage upon inflammasome activation, but rather promotes GSDMD oligomerization in the plasma membrane. Defects in GSDMD oligomerization and pore formation can be rescued by mitochondrial poisons that stimulate reactive oxygen species (ROS) production, and ROS modulation impacts the ability of inflammasome pathways to promote pore formation downstream of GSDMD cleavage. These findings reveal an unexpected link between key regulators of immunity (inflammasome-GSDMD) and metabolism (Ragulator-Rag).
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1 retracted
RETRACTED: mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation
Moon, J.-S., Hisata, S., Park, M.-A., DeNicola, G. M., Ryter, S. W., Nakahira, K., & Choi, A. M. K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.046 · Cited by 374
RetractedCleavage of GSDMD by inflammatory caspases determines pyroptotic cell death
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A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602
Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9
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Self-citationCaspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Kayagaki, N., Stowe, I. B., Lee, B. L., O’Rourke, K., Anderson, K., Warming, S., Cuellar, T., Haley, B., Roose-Girma, M., Phung, Q. T., et al. (2015) · Nature · doi:10.1038/nature15541 · Cited by 3,686
Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
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Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin
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Pore-forming activity and structural autoinhibition of the gasdermin family
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Cited by
Role of pyroptosis in inflammation and cancer
Wei, X., Xie, F., Zhou, X., Wu, Y., Yan, H., Liu, T., Huang, J., Wang, F., Zhou, F., & Zhang, L. (2022) · Cellular & Molecular Immunology · doi:10.1038/s41423-022-00905-x · Cited by 699
A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases
Barnett, K. C., Li, S., Liang, K., & Ting, J. P.-Y. (2023) · Cell · doi:10.1016/j.cell.2023.04.025 · Cited by 458
Regulated cell death in myocardial ischemia–reperfusion injury
Xiang, Q., Yi, X., Zhu, X.-H., Wei, X., & Jiang, D.-S. (2024) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.10.010 · Cited by 448
Chen, Y., Luo, R., Li, J., Wang, S., Ding, J., Zhao, K., Lu, B., & Zhou, W. (2022) · ACS Nano · doi:10.1021/acsnano.1c08913 · Cited by 177
Bradfield, C. J., Liang, J. J., Ernst, O., John, S. P., Sun, J., Ganesan, S., de Jesus, A. A., Bryant, C. E., Goldbach-Mansky, R., & Fraser, I. D. C. (2023) · Cell Death & Differentiation · doi:10.1038/s41418-022-01106-9 · Cited by 33
Metadata
- Authors
- Evavold, C. L., Hafner-Bratkovič, I., Devant, P., D’Andrea, J. M., Ngwa, E. M., Boršić, E., Doench, J. G., LaFleur, M. W., Sharpe, A. H., Thiagarajah, J. R., & Kagan, J. C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 184
- Issue
- 17
- Pages
- 4495-4511.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W3186520869
- Cited by
- 417
- References
- 80
- FWCI
- 19.99
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway. https://app.cochat.ai/papers/10.1016/j.cell.2021.06.028
- The paper
- Evavold, C. L., Hafner-Bratkovič, I., Devant, P., D’Andrea, J. M., Ngwa, E. M., Boršić, E., Doench, J. G., LaFleur, M. W., Sharpe, A. H., Thiagarajah, J. R., & Kagan, J. C. (2021). Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway. Cell. https://doi.org/10.1016/j.cell.2021.06.028
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
