Related Experiment Video

Updated: Aug 21, 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

10.8K

CDC42 regulates PYRIN inflammasome assembly

Lotte Spel1, Lea Zaffalon1, Cyrielle Hou1

  • 1Department of Immunobiology, University of Lausanne, 155 Ch. des Boveresses, 1066 Epalinges, Switzerland.

Cell Reports
|November 17, 2022
PubMed

Insights

The PYRIN inflammasome pathway, crucial for immunity, can cause autoinflammation when overactive. This study identifies CDC42 as essential for PYRIN inflammasome assembly and function in autoinflammatory diseases.

Area of Science:

  • Immunology
  • Cell Biology
  • Genetics

Background:

  • The PYRIN inflammasome is integral to innate immunity against pathogens.
  • Dysregulated PYRIN inflammasome activation causes autoinflammation, exemplified by familial Mediterranean fever (FMF).
  • Molecular mechanisms governing PYRIN inflammasome assembly, including dephosphorylation and oligomerization, remain unclear.

Purpose of the Study:

  • To identify novel regulators of PYRIN inflammasome function using a functional genetics approach.
  • To elucidate the role of the small Rho GTPase CDC42 in PYRIN inflammasome activation and assembly.

Main Methods:

  • Functional genetics screen to identify PYRIN inflammasome regulators.
  • Analysis of CDC42's impact on PYRIN activity, phosphorylation, and inflammasome complex oligomerization.

Main Results:

  • CDC42 was identified as essential for PYRIN inflammasome activity and oligomerization.
  • CDC42's catalytic activity inhibits PYRIN via phosphorylation, but its inflammasome-supportive role is independent of GDP/GTP binding.
  • CDC42's function in inflammasome assembly does not involve PYRIN dephosphorylation.

Conclusions:

  • CDC42 plays a dual role in regulating PYRIN inflammasome pathway.
  • CDC42 is a critical component required for PYRIN inflammasome assembly in both physiological and pathological conditions.
  • These findings offer new insights into the molecular basis of autoinflammatory diseases driven by PYRIN inflammasome dysregulation.
Keywords:
CDC42CP: ImmunologyFMFMEFVNOCARHPAANDPYRINRhoAinflammasomesmall GTPase

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.3K
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

21.0K

Related Concept Videos

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...
9.1K
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.4K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
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...
2.5K
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...
6.5K