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Updated: Oct 19, 2025

High-throughput Measurement of Plasma Membrane Resealing Efficiency in Mammalian Cells
Published on: January 7, 2019
Regulation of Lytic and Non-Lytic Functions of Gasdermin Pores
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Abstract:
Pyroptosis is a necrotic form of cell death that was initially found to be induced upon activation of inflammatory caspases by inflammasome complexes. Mechanistically, pyroptosis induction requires cleavage of the caspase substrate gasdermin D (GSDMD), and the release of the GSDMD N-terminal fragment, which targets the plasma membrane to form large β-barrel pores. GSDMD shares this pore-forming ability with other gasdermin family members, which induce pyroptosis during infection or upon treatment with chemotherapy drugs. While induction of cell death has been assumed to be the main function of the gasdermin pores, increasing evidence suggests that these pores have non-lytic functions, such as in releasing cytokines or alarmins and in regulating intracellular signaling via ionic fluxes. Here we discuss how gasdermin pore formation is regulated to induce membrane permeabilization or lysis, how gasdermin pores achieve specificity for cargo-release and how cells repair gasdermin-induced damage to the plasma membrane.
Insights
Pyroptosis, a cell death form, involves gasdermin D (GSDMD) pores. These pores, beyond cell death, release signaling molecules and regulate cell functions.
Area of Science:
- Cellular biology
- Immunology
- Molecular mechanisms of cell death
Background:
- Pyroptosis is inflammatory cell death mediated by inflammasomes and caspases.
- Gasdermin D (GSDMD) cleavage and N-terminal fragment pore formation are central to pyroptosis.
- Gasdermin family members induce cell death during infection and chemotherapy.
Purpose of the Study:
- To explore the non-lytic functions of gasdermin pores.
- To discuss the regulation of gasdermin pore formation and membrane permeabilization.
- To examine cargo-release specificity and cellular repair mechanisms for gasdermin-induced damage.
Main Methods:
- Review of existing literature on pyroptosis and gasdermin family.
- Analysis of molecular mechanisms of gasdermin pore formation.
- Discussion of cellular responses to gasdermin-mediated membrane damage.
Main Results:
- Gasdermin pores facilitate non-lytic functions, including cytokine release and regulation of signaling via ionic fluxes.
- Regulation of gasdermin pore formation controls membrane permeabilization versus lysis.
- Gasdermin pores exhibit specificity in cargo release.
- Cells possess mechanisms to repair gasdermin-induced plasma membrane damage.
Conclusions:
- Gasdermin pores have diverse roles beyond cell death, impacting cellular signaling and tissue homeostasis.
- Understanding gasdermin pore regulation is crucial for therapeutic targeting in inflammatory diseases and cancer.
- Cellular repair mechanisms highlight the dynamic interplay between gasdermin activity and cell survival.
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