Figure 7. Model for GSDMD‐mediated pyroptotic cell death.
Canonical inflammasomes act as sensors for a variety of pathogens and cellular insults. Assembly of these types of inflammasomes involves multimerization of the receptor (purple), which initiates filament formation of the adaptor protein ASC (green). ASC filaments act as activation platforms for caspase‐1 (blue). In the noncanonical pathway, LPS is directly bound by caspase‐11 (yellow), resulting in its activation. Caspase‐1 processes interleukin IL‐1β (red). Both caspase‐1 and caspase‐11 process GSDMD (orange), which results in release of the GSDMDNterm fragment. GSDMDNterm forms a large pore in the plasma membrane. Pore formation results in rapid loss of membrane integrity, the dissipation of the electrochemical gradient, and ultimately in cell death.