Figure 3.

Model of LtxA-mediated cell death in lymphocytes. LtxA induces clustering of LFA-1 in the lipid rafts, where LFA-1 colocalizes strongly with Fas. After association with LFA-1, LtxA partially transverses the cell membrane and interacts with membrane proximal domains of LFA-1, interfering with its activation. The literature supports that LtxA only interacts with LFA-1 1, but it is possible that LtxA interacts with LFA-1 and Fas independently 2. or LtxA simultaneously interacts with both LFA-1 and Fas 3. Faulty activation of LFA-1 may allow the β₂ tail to either directly activate caspase-8 or to signal via the Fas-mediated cell death pathway. The activation of caspase-8 can result in perturbation of the mitochondrial membrane, releasing cytochrome c into the cytosol, or further activation of effector caspases. Both pathways culminate in cell death.