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

Area of Science:

• Cell Biology
• Parasitology
• Biophysics

Background:

• Actin-based motility is crucial for malaria parasite transmission.
• Filamentous actin has not been directly visualized within malaria parasites.
• Understanding actin dynamics is key to understanding parasite movement.

Purpose of the Study:

• To visualize and characterize dynamic actin filaments within Plasmodium falciparum sporozoites.
• To determine the assembly, path, and fate of actin filaments during parasite gliding.
• To generate a complete 3D model of filamentous actin in sporozoites.

Main Methods:

• Focused ion beam milling combined with electron cryo-tomography.
• In situ cryo-electron tomography of unperturbed Plasmodium falciparum cells.
• 3D reconstruction and analysis of filamentous actin structures.

Main Results:

• Micrometer-long actin filaments were observed, exceeding in vitro estimates.
• Actin filaments assemble at the apical end, grow during transport via the glideosome, and disassemble at the basal end.
• Pores in the Inner Micronemal Complex (IMC) at the basal end may facilitate actin recycling.
• Actin bundles were also observed within the parasite nucleus.

Conclusions:

• This study provides the first direct visualization of dynamic actin filaments in malaria sporozoites.
• The findings reveal a detailed model of actin dynamics essential for parasite motility and transmission.
• The observed actin structures and dynamics offer new insights into the glideosome mechanism and potential transmission-blocking strategies.