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

• Final Report Year: 2025

Final Report Abstract

The gliding motility of apicomplexan parasites is essential for the progression through their highly complex life cycles and is based on an actin-myosin motor. Apicomplexans only express a small set of actin-binding proteins, one of which is coronin, which regulates F-actin. Coronins are involved in various cellular processes in different eukaryotes, such as cell motility and signal transduction. They consist of one or two WD40 repeat-containing beta-propellers that mediate interactions with actin filaments , a unique region allowing interaction with a range of different proteins and a C-terminal coiled coil domain important for oligomerization and localization to membranes In Plasmodium, the causing agent of malaria, one coronin isoform has been identified and shown to bind to and crosslink actin filaments. In our applications, we aimed to compare the two coronins from P. falciparum and P. berghei, with a particular focus on domain specific functions. This investigation led to the identification of a potential second actin-binding site within the C-terminus, which we demonstrated plays a crucial role in Plasmodium sporozoite motility. Using orbital TIRF microscopy as well as laser tweezer experiments we could show that coronin is needed for modulating adhesive strength as coronin(-) as wells as mutants of two conserved actin-binding sites are crucial for 2D motility.

Publications

• Inter-subunit interactions drive divergent dynamics in mammalian and Plasmodium actin filaments. PLOS Biology, 16(7), e2005345.
  Douglas, Ross G.; Nandekar, Prajwal; Aktories, Julia-Elisabeth; Kumar, Hirdesh; Weber, Rebekka; Sattler, Julia M.; Singer, Mirko; Lepper, Simone; Sadiq, S. Kashif; Wade, Rebecca C. & Frischknecht, Friedrich
  
• Still running fast: Plasmodium ookinetes and sporozoites 125 years after their discovery. Trends in Parasitology, 39(12), 991-995.
  Singer, Mirko & Frischknecht, Friedrich
  
• Cytoskeletal dynamics in parasites. Current Opinion in Cell Biology, 86, 102277.
  Reber, Simone; Singer, Mirko & Frischknecht, Friedrich
  
• Overcoming the egress block of Plasmodium sporozoites expressing fluorescently tagged circumsporozoite protein. Molecular Microbiology, 121(3), 565-577.
  Thieleke‐Matos, Carolina; Walz, Kevin; Frischknecht, Friedrich & Singer, Mirko
  
• Traction force generation in motile malaria parasites is modulated by the Plasmodium adhesin TLP. openRxiv.
  Ripp, Johanna; Probst, Dimitri; Singer, Mirko; Schwarz, Ulrich S. & Frischknecht, Friedrich
  
• An atypical Arp2/3 complex is required for Plasmodium DNA segregation and malaria transmission. Nature Microbiology, 10(7), 1775-1790.
  Hentzschel, Franziska; Jewanski, David; Sokolowski, Yvonne; Agarwal, Pratika; Kraeft, Anna; Hildenbrand, Kolja; Dorner, Lilian P.; Singer, Mirko; Marti, Matthias & Frischknecht, Friedrich
  
• Three-Dimensional Chiral Active Ornstein-Uhlenbeck Model for Helical Motion of Microorganisms. Physical Review Letters, 135(12).
  Lettermann, Leon; Ziebert, Falko; Singer, Mirko; Frischknecht, Friedrich & Schwarz, Ulrich S.