Complex eukaryotic-like actin regulation systems from Asgard archaea

Abstract

Asgard archaea genomes contain potential eukaryotic-like genes that provide intriguing insight for the evolution of eukaryotes. The actin polymerization/depolymerization cycle is critical for providing force and structure for a variety of processes in eukaryotes, including membrane remodelling. Here, we identify actin filament severing, capping, annealing and bundling, and monomer sequestration activities by gelsolin proteins from Thorarchaeota (Thor), which complete a eukaryote-like actin depolymerization cycle. Thor gelsolins are comprised of one or two copies of the prototypical gelsolin domain and appear to be a record of an initial pre-eukaryotic gene duplication event, since eukaryotic gelsolins are generally comprised of three to six domains. X-ray crystal structure determination of these proteins in complex with mammalian actin revealed similar interactions to the first domain of human gelsolin. Asgard two-domain, but not one-domain, gelsolins contain calcium-binding sites, which is manifested in calcium-controlled activities. Expression of two-domain gelsolins in mammalian cells led to enhanced actin filament disassembly on ionomycin-triggered calcium release. This functional demonstration, at the cellular level, provides evidence for calcium-regulated actin cytoskeleton in Asgard archaea, and indicates that the calcium-regulated actin cytoskeleton predates eukaryotes. In eukaryotes, dynamic bundled filaments are responsible for shaping filopodia and microvilli. By correlation, the formation of the protrusions observed from Lokiarchaeota cell bodies may involve gelsolin-regulated actin structures.