Toxoplasma gondiiactin filaments are tuned for rapid disassembly and turnover

Abstract

AbstractThe cytoskeletal protein actin plays a critical role in the pathogenicity ofToxoplasma gondii, mediating invasion and egress, cargo transport, and organelle inheritance. Advances in live cell imaging have revealed extensive filamentous actin networks in the Apicomplexan parasite, but there is conflicting data regarding the biochemical and biophysical properties ofToxoplasmaactin. Here, we imaged thein vitroassembly of individualToxoplasmaactin filaments in real time, showing that native, unstabilized filaments grow tens of microns in length. Unlike skeletal muscle actin,Toxoplasmafilaments intrinsically undergo rapid treadmilling due to a high critical concentration, fast monomer dissociation, and rapid nucleotide exchange. Cryo-EM structures of stabilized and unstabilized filaments show an architecture like skeletal actin, with differences in assembly contacts in the D-loop that explain the dynamic nature of the filament, likely a conserved feature of Apicomplexan actin. This work demonstrates that evolutionary changes at assembly interfaces can tune dynamic properties of actin filaments without disrupting their conserved structure.