On the evolutionary trajectories of signal-transducing amyloids in fungi and beyond

In the last decade, multiple reports have established that amyloids can bear important functional roles in a variety of biological processes and in distant taxonomic clades. In filamentous fungi, amyloids are involved in a signal transducing mechanism in which a group of NOD-like receptors (NLRs) controls downstream effector proteins to induce a programmed cell death reaction. A structurally characterized example of fungal signal-transducing amyloid is the prion-forming domain (PFD) of the HET-S toxin from Podospora anserina. Amyloid-mediated programmed cell death is equally reported in metazoans in the context of innate immunity and antiviral response. The cell death reaction, described as programmed necrosis, is dependent on an amyloid-forming RHIM motif (RIP homotypic interaction motif). An evolutionary link between the RHIM and the PFD signaling amyloids has been previously reported. Our recent study ties further the signaling amyloids in fungi and metazoans, reporting a fungal signal-transducing domain with amyloid and prion-like properties, which shows significant sequence similarity to the metazoan RHIM motif. Here, I discuss the expanding class of the signal-transducing amyloids and reflect on the possible evolutionary scenarios of their diversification.