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Title

Characterization of a new response to bacterial pore-forming toxin that promotes cell survival in a caspase-1 dependent activation of SREBPs
Author
Gurcel, Laure
Director
Van Der Goot Grunberg, Françoise G.
Defense Thèse de doctorat : Univ. Genève, 2006 - Sc. 3801 - 2006/10/16
Abstract Many pathogenic organisms produce poreforming 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.
Keywords SREBP — Cell survival — Caspase-1 — Pore-forming toxin — Aerolysin — Lipid metabolism — Innate immunity — Nod-like receptor — Inflammasome — Potassium efflux
Identifiers
URN: urn:nbn:ch:unige-4355
Note Texte en anglais avec résumé en français
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Thesis - public document Free access
Structures
Faculté des sciences / Section de chimie et biochimie / Département de biochimie
Citation
(ISO format) 		GURCEL, Laure. Characterization of a new response to bacterial pore-forming toxin that promotes cell survival in a caspase-1 dependent activation of SREBPs. Université de Genève. Thèse, 2006. doi: 10.13097/archive-ouverte/unige:435 https://archive-ouverte.unige.ch/unige:435

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Deposited on : 2008-10-29

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