The Ras GTPase-activating-like protein IQGAP1 bridges Gasdermin D to the ESCRT system to promote IL-1β release via exosomes.

ABSTRACT: 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

SUBMITTER: Liao Y 

PROVIDER: S-EPMC9811620 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature