| Autor: |
Yun, Liao, Xing, Chen, William, Miller-Little, Han, Wang, Belinda, Willard, Katarzyna, Bulek, Junjie, Zhao, Xiaoxia, Li |
| Rok vydání: |
2022 |
| Zdroj: |
The EMBO journalReferences. 42(1) |
| ISSN: |
1460-2075 |
| Popis: |
IL-1β can exit the cytosol as an exosomal cargo following inflammasome activation in intestinal epithelial cells (IECs) in a Gasdermin D (GSDMD)-dependent manner. The mechanistic connection linking inflammasome activation and the biogenesis of exosomes has so far remained largely elusive. Here, we report the Ras GTPase-activating-like protein IQGAP1 functions as an adaptor, bridging GSDMD to the endosomal sorting complexes required for transport (ESCRT) machinery to promote the biogenesis of pro-IL-1β-containing exosomes in response to NLPR3 inflammasome activation. We identified IQGAP1 as a GSDMD-interacting protein through a non-biased proteomic analysis. Functional investigation indicated the IQGAP1-GSDMD interaction is required for LPS and ATP-induced exosome release. Further analysis revealed that IQGAP1 serves as an adaptor which bridges GSDMD and associated IL-1β complex to Tsg101, a component of the ESCRT complex, and enables the packaging of GSDMD and IL-1β into exosomes. Importantly, this process is dependent on an LPS-induced increase in GTP-bound CDC42, a small GTPase known to activate IQGAP1. Taken together, this study reveals IQGAP1 as a link between inflammasome activation and GSDMD-dependent, ESCRT-mediated exosomal release of IL-1β. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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