Plasmodium coronin function during malaria parasite migration

• Applicant: Professor Dr. Friedrich Frischknecht
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Cell Biology
• Term: from 2016 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 298742814

Coronins are a family of actin-binding proteins that harbor one or two WD40 repeat-containing beta-propellers to mediate binding to actin filaments. They can also contain a number of additional domains and regions in their C-terminal half that allow interaction with a range of different proteins including actin, actin-binding proteins and microtubules and can mediate oligomerization. Hence different coronins often mediate distinct functions. Coronin from the protozoan, human-infecting parasite Plasmodium falciparum was identified and characterized as an actin filament-binding protein and coronin in the rodent-infecting parasite P. berghei was shown to be important for effective motility of sporozoites, the highly motile forms of the parasite transmitted by mosquitoes. We previously showed that P. berghei coronin function is at least partly localized in the WD40 domain. During the previous funding period we identified a new site in the C-terminus of P. berghei coronin that is additionally important in coronin function probably due to actin filament-binding. Deleting either the C- or N-terminal half of coronin furthermore showed a previously not observed motility phenotype in sporozoites suggesting a cooperative function of both halves of the protein. We now aim at understanding the mechanistic basis for these phenotypes by (i) expressing both parts of the protein as well as full-length coronin in wild type and mutant forms and investigating their capacity to bind actin filaments in vitro, (ii) investigating the localization of mutant proteins fused with a fluorescent protein in parasites expressing a fluorescent nanobody that labels specifically actin filaments and (iii) investigating force generation and adhesion dynamics using optical tweezers and surface sensitive imaging of the different parasite lines.

• DFG Programme: Research Grants