Caspases come together over LPS

Abstract

Caspases are cellular executors, initiating cell death. In a recent study, Shi et al. report that caspases 4/5/11 are cytosolic LPS receptors, becoming activated through oligomerization upon interaction with LPS. These findings shed new light on the mechanisms underlying caspase-mediated pyroptosis, and have implications for the development of effective drugs to treat sepsis.

Figure 1

A schematic overview of LPS-induced caspase-4/5/11 activation. Shi et al. have demonstrated that LPS (green) binds to the CARD domain (purple) of caspase-4/5/11 (red), inducing its oligomerization and consequential proteolytic cleavage. Upon activation, caspase-4/5/11 (yellow) may cause pyroptosis and cell death, or inflammation through caspase-1. In the box, we speculate that the positively charged residues present in the caspase CARD domain may interact with the negatively charged LPS lipid head group. Once multiple caspase molecules are localized to the micelle, their induced proximity may result in auto-activation of the caspase to its active, oligomeric state.