Figure 2.

Pathways involved in C. perfringens beta-toxin (CPB) intracellular action. CPB structure was predicted by the SwissModel online software (Genbank ID: L13198) using standard settings. Initial binding of CPB to its potential receptor, the ATP-gated P2X₇ receptor, induces a rapid peak of ATP release from target cells. This ATP loss is not associated with cell lysis and it would occur through the ATP-release channel pannexin 1. The released ATP would stimulate further CPB binding and oligomer formation, facilitating the pore-forming activity of the toxin. Pore formation results in Ca²⁺ influx and loss of intracytoplasmic K⁺ (iK⁺). Increase of iCa²⁺ is associated with calpain activation and necroptosis, which is inhibited by Nec-1; only low levels of caspase-3 activation occurs, suggesting that apoptosis is not a significant mechanism of cell death. Decrease iK⁺ is associated with the activation of MAPK and JNK, which activate host cell survival and defense pathways. Dashed red arrows represent what is concluded and/or suggested by the current authors. A dashed black arrow shows direction of movement.