Poster Presentation The 48th Lorne Conference on Protein Structure and Function 2023

Repurposing the Plasmodium falciparum mitosis mechanism to drive cellular elongation and chromosomes reorganization in gametocytes (#357)

Jiahong Li 1 , Gerald J. Shami 1 , Ellie Cho 1 2 , Boyin Liu 1 , Eric Hanssen 1 3 , Matthew W.A. Dixon 4 5 , Leann Tilley 1
  1. Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia
  2. Biological Optical Microscopy Platform, The University of Melbourne, Parkville, VIC, Australia
  3. Ian Holmes Imaging Center, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia
  4. Department of Infectious Diseases, The Peter Doherty Institute, The University of Melbourne, Parkville, VIC, Australia
  5. Walter and Eliza Hall Institute, Parkville, VIC, Australia

Plasmodium falciparum is the most prevalent and fatal species among human malaria parasites. The parasite has a complex lifecycle that involves both asexual and sexual stages in its human host. The sexual stage gametocytes adopt a falciform shape driven by the assembly of a network of microtubules, anchored onto the inner membrane complex (IMC). Applying optical and electron microscopy, we show that a non-mitotic microtubule organizing center (MTOC) is embedded in the gametocyte nuclear membrane. It orients the endoplasmic reticulum and the nascent IMC and seeds cytoplasmic microtubules in early-stage gametocyte development. A dense bundle of microtubules stretches into the nuclear lumen, elongating and distorting the nuclear envelope and capturing and organizing the chromatin. The classical components associated with mitosis mechanism, including the centriolar plaque proteins, Pfcentrin-1 and -4, the microtubule-associated protein, End Binding protein-1, PfEB1, the kinetochore protein, PfNDC80 and the centromere-associated protein, PfCENH3, are involved in the assembly/disassembly process. Depolymerization of microtubules by trifluralin disrupts the cell elongation and disorganises the chromatin, centromere and kinetochore organization, indicating that this unusual non-mitotic hemispindle plays a vital role in chromatin organization, IMC positioning and subpellicular microtubule formation during gametocyte development.