Related Experiment Video

Updated: Oct 28, 2025

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
06:52

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages

Published on: May 21, 2018

10.9K

DPP9 holds all the CARD8s for inflammasome regulation

Julia Wegner1, Alexander Kirchhoff1, Martin Schlee1

  • 1Department of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, D-53127 Bonn, Germany.

Immunity
|July 14, 2021
PubMed

Insights

The enzyme dipeptidyl peptidase 9 (DPP9) prevents the CARD8 inflammasome from activating by binding to its C-terminal fragment. This interaction inhibits pyroptosis, a form of programmed cell death, in response to pathogen proteases.

Area of Science:

  • Innate immunity
  • Inflammasome biology
  • Cell death pathways

Background:

  • CARD8 (Caspase recruitment domain-containing protein 8) is a sensor of pathogen-associated protease activity.
  • CARD8 activation leads to the assembly of a pyroptosis-inducing inflammasome.
  • The precise regulatory mechanisms controlling CARD8 inflammasome activation are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which CARD8 inflammasome activation is regulated.
  • To identify the specific interactions that prevent premature or inappropriate inflammasome assembly.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine high-resolution structures.
  • Biochemical assays to assess protein-protein interactions and enzymatic activity.

Main Results:

  • DPP9 (Dipeptidyl peptidase 9) directly binds to the C-terminal fragment of CARD8.
  • This binding event sequesters the CARD8 fragment, preventing its incorporation into the inflammasome complex.
  • DPP9 acts as a negative regulator, suppressing CARD8-mediated pyroptosis.

Conclusions:

  • DPP9 is a key inhibitor of the CARD8 inflammasome.
  • Understanding the DPP9-CARD8 interaction provides insights into the control of pyroptosis.
  • This mechanism highlights a critical checkpoint in innate immune sensing of pathogens.

More Related Videos

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

21.1K
Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

2.7K

Related Concept Videos

IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
13.0K
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
9.2K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.9K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.7K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.7K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.9K