Molecular architecture of glideosome and nuclear F-actin in Plasmodium falciparum

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Abstract
Actin-based motility is required for the transmission of malaria sporozoites. While this has been shown biochemically, filamentous actin has remained elusive and has not been directly visualised inside the parasite. Using focused ion beam milling and electron cryo-tomography, we studied dynamic actin filaments in unperturbed Plasmodium falciparum cells for the first time. This allowed us to dissect the assembly, path and fate of actin filaments during parasite gliding and determine a complete 3D model of F-actin within sporozoites. We observe micrometre long actin filaments, much longer than expected from in vitro studies. After their assembly at the parasite’s apical end, actin filaments continue to grow as they are transported down the cell as part of the glideosome machinery, and are disassembled at the basal end in a rate-limiting step. Large pores in the IMC, constrained to the basal end, may facilitate actin exchange between the pellicular space and cytosol for recycling and maintenance of directional flow. The data also reveal striking actin bundles in the nucleus. Implications for motility and transmission are discussed.
Funding Information
  • DFG (INST 152/ 772-1, 774-1, 775-1, 777-1 FUGG)
  • Human Frontier Science Program (LT000024/2020-L)
  • Wellcome Trust (227774/Z/23/Z)
  • Wellcome Trust (107806/Z/15/Z)
  • Wellcome Trust (209250/Z/17/ Z)
  • Hessian Excellence Program
  • Horizon 2020 Framework Programme (731060)

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