Characterization of a new response to bacterial pore-forming toxin that promotes cell survival in a caspase-1 dependent activation of SREBPs

Diplôme Thèse Characterization of a new response to bacterial pore-forming toxin that promotes cell survival in a caspase-1 dependent activation of SREBPs eng 2006-10-16 author Gurcel Laure 559486 director Van Der Goot Grunberg Françoise G. 24466 10.13097/archive-ouverte/unige:435 urn:nbn:ch:unige-4355 Sc. 3801 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. SREBP Cell survival Caspase-1 Pore-forming toxin Aerolysin Lipid metabolism Innate immunity Nod-like receptor Inflammasome Potassium efflux Dewey 540 39 Département de biochimie 144 false e573354f-75c7-46d3-844f-39230046daff Thesis Public file1.pdf 4114424 application/pdf openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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Characterization of a new response to bacterial pore-forming toxin that promotes cell survival in a caspase-1 dependent activation of SREBPs				2006	945	694

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Gurcel, Laure