Related Experiment Video

Updated: Mar 18, 2026

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

11.3K

Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores

Xing Liu1,2, Zhibin Zhang1,2, Jianbin Ruan1,3

  • 1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.

Nature
|July 8, 2016
PubMed

Insights

Gasdermin D N-terminal fragment (GSDMD-NT) forms pores in cell membranes, causing pyroptosis and cytokine release. This GSDMD-NT fragment exhibits direct antibacterial activity, potentially impacting host defense mechanisms.

Area of Science:

  • Cellular Biology
  • Immunology
  • Microbiology

Background:

  • Inflammatory caspases activate in response to infection and danger signals.
  • Activated caspases cleave gasdermin D (GSDMD), producing GSDMD-NT, which induces pyroptosis and cytokine release.
  • The mechanism by which GSDMD-NT induces cell death was previously unknown.

Purpose of the Study:

  • To elucidate the mechanism of GSDMD-NT-induced cell death.
  • To investigate the membrane-binding properties and pore-forming activity of GSDMD-NT.
  • To determine the role of GSDMD-NT in host defense against microbial infection.

Main Methods:

  • Electron microscopy to visualize GSDMD-NT oligomerization and pore formation.
  • Lipid-binding assays to identify GSDMD-NT interaction partners.
  • Site-directed mutagenesis to assess the role of specific residues in GSDMD-NT function.
  • In vitro assays to evaluate GSDMD-NT bactericidal activity.

Main Results:

  • GSDMD-NT oligomerizes in membranes, forming pores visible by electron microscopy.
  • GSDMD-NT binds to phosphatidylinositol phosphates, phosphatidylserine, and cardiolipin.
  • Mutations in conserved basic residues abolish GSDMD-NT oligomerization, membrane binding, pore formation, and pyroptosis.
  • GSDMD-NT exhibits selective toxicity towards intracellular components and bacteria, sparing neighboring host cells.

Conclusions:

  • GSDMD-NT induces pyroptosis by forming membrane pores.
  • GSDMD-NT's lipid-binding properties dictate its cell-killing specificity.
  • GSDMD-NT possesses direct bactericidal activity, contributing to host defense, though its in vivo significance requires further investigation.

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

3.9K
Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum06:12

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

3.6K

Related Concept Videos

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...
9.2K
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...
9.1K
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...
15.7K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
7.1K
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...
14.5K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
5.5K