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Review
. 2022 Jul 1;14(7):a041061.
doi: 10.1101/cshperspect.a041061.

Inflammasomes and Other Caspase-Activation Platforms

Douglas R Green  1
Affiliations
Review

Inflammasomes and Other Caspase-Activation Platforms

Douglas R Green. Cold Spring Harb Perspect Biol. .
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Cytosolic lipopolysaccharide (LPS) directly induces caspases and pyroptosis. This appears to be restricted to caspase-4 and caspase-5 in humans and caspase-11 in mice. Other caspases we have discussed are not activated in this direct manner.
Figure 2.
Figure 2.
The basic inflammasome and activation of caspase-1.
Figure 3.
Figure 3.
Overexpression of ASC can activate caspase-1. This is not a physiological mechanism of caspase-1 activation, but the observation is informative.
Figure 4.
Figure 4.
General structure of inflammasomes. 1. The intracellular receptor, containing a pyrin domain (PYD), on interaction with its ligand forms a disc-like structure. 2. The center of this structure interacts with ASC through PYD–PYD interactions. 3. The PYD domains of ASC interact with additional ASC PYD domains to form a cylindrical structure. 4. The CARD domains of caspase-1 monomers bind to the CARD of ASC. 5. Bound caspase-1 recruits additional caspase-1 molecules through CARD–CARD interactions, forming a fibril. A “mature” inflammasome is shown in Figure 5.
Figure 5.
Figure 5.
Inflammasomes have fibrils of caspase-1.
Figure 6.
Figure 6.
Some TLRs and the PAMPs that activate them.
Figure 7.
Figure 7.
Some NLRs that function in inflammasomes. The PAMPs and DAMPs that induce them are listed. Toxins from bacteria can also alter potassium levels, thereby indirectly facilitating inflammasome formation.
Figure 8.
Figure 8.
Activation of the NLRP3 inflammasome.
Figure 9.
Figure 9.
Inert crystals induce the NLRP3 inflammasome in gout and other diseases. (Bottom left, Reprinted from Gillray 1799.)
Figure 10.
Figure 10.
Activation of the NLRC4 inflammasome.
Figure 11.
Figure 11.
Two models of the NLRP1 inflammasome. Both may be correct in different settings.
Figure 12.
Figure 12.
The AIM2 inflammasome. This is a simplified scheme, and AIM2 facilitates the formation of caspase-1 fibrils, as we saw for other inflammasomes.
Figure 13.
Figure 13.
APAF1 is in the Nod-like receptor (NLR) family.
Figure 14.
Figure 14.
Return of the just-so story.
Figure 15.
Figure 15.
The PIDDosome activates caspase-2. DD, death domain.
Figure 16.
Figure 16.
PIDDosome structure. The interactions of PIDD (P) and RAIDD (R) DDs are shown on the right. (Left, PDB 2OF5 [Park et al. 2007]; right, reprinted from Park et al. 2007, ©2007 with permission from Elsevier.)
Figure 17.
Figure 17.
Fluorescence micrograph showing how PIDD localizes to mature centrosomes. PIDD (green) associates with the mature centrosome (which also contains CEP164, blue). The nascent (upper red spot) and mature centrosomes (lower complex of spots) both contain CP110 (red). The lower image is a magnified view of the area enclosed by the white square in the upper image. (Photo courtesy of Dr. Luca Fava and Dr. Andreas Villunger, University of Innsbruck.)
Figure 18.
Figure 18.
Aberrant extra mature centrosomes activate caspase-2. During the S/G2 phases of the cell cycle, the centrosome duplicates, but PIDD remains associated with only the mature centrosome. If cytokinesis fails, leading to the formation of a tetraploid cell in the following G1 phase, two mature centrosomes appear in the cell, leading to PIDD–PIDD interaction, recruitment of RAIDD, and activation of caspase-2.
See this image and copyright information in PMC

References

    1. Green DR. 2022. a. The mitochondrial pathway of apoptosis, Part 1: MOMP and beyond. Cold Spring Harb Perspect Biol 10.1101/cshperspect.a041038 - DOI - PMC - PubMed
    1. Green DR. 2022. b. The death receptor pathway of apoptosis. Cold Spring Harb Perspect Biol 10.1101/cshperspect.a041053 - DOI - PMC - PubMed
    1. Green DR. 2022. c. Nonapoptotic cell death pathways. Cold Spring Harb Perspect Biol 10.1101/cshperspect.a041079 - DOI - PMC - PubMed
    1. Green DR. 2022. d. Caspase activation and inhibition. Cold Spring Harb Perspect Biol 10.1101/cshperspect.a041020 - DOI - PMC - PubMed
    1. Green DR. 2022. e. The mitochondrial pathway of apoptosis, Part II: the BCL-2 protein family. Cold Spring Harb Perspect Biol 10.1101/cshperspect.a041046 - DOI - PMC - PubMed

FIGURE CREDITS

    1. Gillray J. 1799. The Gout. [Etching]
    1. Park HH, Logette E, Raunser S, Cuenin S, Walz T, Tschopp J, Wu H. 2007. Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex. Cell 128: 533–546. 10.1016/j.cell.2007.01.019 - DOI - PMC - PubMed

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