Caspase-1 Activation of Lipid Metabolic Pathways in Response to Bacterial Pore-Forming Toxins Promotes Cell Survival
| Autor: | Jürg Tschopp, Laurence Abrami, Laure Gurcel, F. Gisou van der Goot, Stephen E. Girardin |
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| Rok vydání: | 2006 |
| Předmět: |
Pore Forming Cytotoxic Proteins
Cell Membrane Permeability Cell Survival Membrane lipids Bacterial Toxins Membrane Lipids/*metabolism Potassium/metabolism Natural/*physiology CHO Cells Bacterial Toxins/*metabolism/pharmacology Biology Bacterial Infections/metabolism/physiopathology General Biochemistry Genetics and Molecular Biology Cell membrane Membrane Lipids Cricetinae Sterol Regulatory Element Binding Protein 2/metabolism medicine Cell Membrane Permeability/drug effects/physiology Animals Humans Cell Membrane/drug effects/*metabolism Cell Survival/physiology Sterol Regulatory Element Binding Proteins Pore-forming toxin Innate immune system Biochemistry Genetics and Molecular Biology(all) Caspase 1 Cell Membrane Immunity Inflammasome Bacterial Infections Immunity Innate Sterol regulatory element-binding protein Cell biology Caspase 1/*metabolism medicine.anatomical_structure Biochemistry Membrane biogenesis Sterol Regulatory Element Binding Proteins/*metabolism Potassium Aeromonas Aeromonas/metabolism Intracellular HeLa Cells Sterol Regulatory Element Binding Protein 2 medicine.drug |
| Zdroj: | Cell. 126:1135-1145 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2006.07.033 |
| Popis: | SummaryMany pathogenic organisms produce pore-forming toxins as virulence factors. Target cells however mount a response to such membrane damage. Here we show that toxin-induced membrane permeabilization leads to a decrease in cytoplasmic potassium, which promotes the formation of a multiprotein oligomeric innate immune complex, called the inflammasome, and the activation of caspase-1. Further, we find that when rendered proteolytic in this context caspase-1 induces the activation of the central regulators of membrane biogenesis, the Sterol Regulatory Element Binding Proteins (SREBPs), which in turn promote cell survival upon toxin challenge possibly by facilitating membrane repair. This study highlights that, in addition to its well-established role in triggering inflammation via the processing of the precursor forms of interleukins, caspase-1 has a broader role, in particular linking the intracellular ion composition to lipid metabolic pathways, membrane biogenesis, and survival. |
| Databáze: | OpenAIRE |
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