The Gasdermins, a Protein Family Executing Cell Death and Inflammation

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2019 Nov 7

PMID 31690840

Citations 638

Authors

Petr Broz

Pablo Pelegrin

Feng Shao

Affiliations

Soon will be listed here.

Abstract

The gasdermins are a family of recently identified pore-forming effector proteins that cause membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. Gasdermins contain a cytotoxic N-terminal domain and a C-terminal repressor domain connected by a flexible linker. Proteolytic cleavage between these two domains releases the intramolecular inhibition on the cytotoxic domain, allowing it to insert into cell membranes and form large oligomeric pores, which disrupts ion homeostasis and induces cell death. Gasdermin-induced pyroptosis plays a prominent role in many hereditary diseases and (auto)inflammatory disorders as well as in cancer. In this Review, we discuss recent developments in gasdermin research with a focus on mechanisms that control gasdermin activation, pore formation and functional consequences of gasdermin-induced membrane permeabilization.

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