Figure 4.
Functional prions in immune signaling. In mammals, receptors such as RIG-I and NLRP3 induce the prion conversion of their respective adaptors MAVS and ASC, which then rapidly polymerize leading to protective cytokine secretion and cell death. In filamentous fungi, a homologous pathway depends on the NWD2 protein, which likely converts the downstream HET-S/s protein into a prion to induce cell death. The fungal NWD2/HET-S/s pathway shares remarkable similarities to the mammalian NLRP3/ASC inflammasome in function and organization. Abbreviations: ASC, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain; CARD, caspase activation and recruitment domain; CTD, C-terminal domain; LLR, leucine-rich repeat; MAVS, mitochondrial antiviral signalling; NLRP3, NLR family, pyrin domain containing 3; RIG-I, retinoic acid-inducible gene I.