Prion-like polymerization as a signaling mechanism

• Beneficial mammalian prions are essential for innate immune signaling.
• Fungi contain similar inflammasome-like pathways that signal through prion conversion.
• Signaling through prion-like conversion offers multicellular organisms unique advantages.
• Prion-like polymerization is a conserved, potentially general mechanism of signal transduction.

The innate immune system uses pattern recognition receptors such as RIG-I and NLRP3 to sense pathogen invasion and other danger signals. Activation of these receptors induces robust signal transduction cascades that trigger the production of cytokines important for host protection. MAVS and ASC are essential adaptor proteins downstream of RIG-I and NLRP3, respectively, and both contain N-terminal domains belonging to the death domain superfamily. Recent studies suggest that both MAVS and ASC form functional prion-like fibers through their respective death domains to propagate downstream signaling. Here, we review these findings, and in this context discuss the emerging concept of prion-like polymerization in signal transduction. We further examine the potential benefits of this signaling strategy, including signal amplification, host evolutionary advantage, and molecular memory.