Faculté des sciences

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

Gurcel, Laure ; Gisou van der Goot, Françoise (Dir.) ; Gruenberg, Jean (Codir.)

Thèse de doctorat : Université de Genève, 2006 ; 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... Plus

Ajouter à la liste personnelle
    Summary
    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.