Dynamics of the Plasmodium Actin Cytoskeleton during Host Cell Invasion

• Applicant: Professor Dr. Kai Matuschewski
• Subject Area: Cell Biology
• Term: from 2003 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5408741

Protozoan parasites of the phylum Apicomplexa include important human and animal pathogens, such as Plasmodium, the etiologic agent of malaria, and Toxoplasma gondii. These facultative intracellular parasites rely on their own actin cytoskeleton for host cell invasion, but the details of this process are unclear. In addition, apicomplexan parasites share a unique mode of actin-dependent locomotion, termed gliding motility that appears to be mechanistically linked to successful host cell invasion. Surprisingly, the majority of literature reports that apicomplexan parasites do not contain actin filaments. This joint project proposes expression of the parasite actin genes in S.cerevisiae for subsequent purification and biochemical analysis. The molecular dynamics of Plasmodium actin polymerization and the role of additional regulatory proteins will be studied for the first time in a heterologous system. In a complementary approach we suggest to employ reverse genetics as well as heterologous gene complementation to study the unique properties of the Plasmodium actin cytoskeleton during host cell entry. A detailed understanding of the regulation of actin filament dynamics and their interactions with motor proteins are fundamental for investigations of the molecular mechanism of Apicomplexan motility and host cell entry.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1150: Signal Pathways to the Cytoskeleton and Bacterial Pathogenesis
• International Connection: Sweden
• Participating Person: Dr. Herwig Schüler