Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes

Abstract

The sexual stage gametocytes of the malaria parasite, Plasmodium falciparum, adopt a falciform (crescent) shape driven by the assembly of a network of microtubules anchored to a cisternal inner membrane complex (IMC). Using 3D electron microscopy, we show that a non-mitotic microtubule organizing center (MTOC), embedded in the parasite’s nuclear membrane, orients the endoplasmic reticulum and the nascent IMC and seeds cytoplasmic microtubules. A bundle of microtubules extends into the nuclear lumen, elongating the nuclear envelope and capturing the chromatin. Classical mitotic machinery components, including centriolar plaque proteins, Pfcentrin-1 and −4, microtubule-associated protein, End-binding protein-1, kinetochore protein, PfNDC80 and centromere-associated protein, PfCENH3, are involved in the nuclear microtubule assembly/disassembly process. Depolymerisation of the microtubules using trifluralin prevents elongation and disrupts the chromatin, centromere and kinetochore organisation. We show that the unusual non-mitotic hemispindle plays a central role in chromatin organisation, IMC positioning and subpellicular microtubule formation in gametocytes.

EB1 decoration of microtubule lattice facilitates spindle-kinetochore lateral attachment inPlasmodiummale gametogenesis

“…EBs are evolutionarily conserved in eukaryotes from yeast to human [27][28][29][30]. In the Plasmodium, EB1 is the only member of this family and it showed a nuclear localization when episomally expressed in the P. falciparum [31], suggesting a role related to the spindle. However, it remains unclear for the precise localization and function of EB1 in the Plasmodium life cycle.…”

Plasmodium falciparum CRK4 links early mitotic events to the onset of S-phase during schizogony

“…S4). We detected Pf SPB at the parasite’s centrosome, also called centriolar plaque, which organizes intranuclear microtubules (Li et al, 2022; Rashpa and Brochet, 2022; Simon et al, 2021). At the centriolar plaque, Pf SPB localized between the extranuclear centrin and the intranuclear tubulin (Fig.…”

A microtubule associated protein is essential for malaria parasite transmission

“…SPMTs of P. falciparum are extremely stable exemplified by their resistance to classic microtubule depolymerizing agents (16). Recent studies showed polyglutamylation of SPMTs in merozoites (17) and gametocytes (13) and suggested its involvement in SPMT stability (17). A second population of microtubules, the spindle microtubules, is necessary to coordinate chromosome segregation and these extend from a single MTOC throughout the nucleus (14, 18).…”

“…In contrast to invasive stages such as sporozoites, merozoites and ookinetes, gametocytes lack apical polarity and an apical polar ring from which SPMTs emanate. A recent study reports the nucleation of SPMTs in gametocytes at the outer centriolar plaque, a non-mitotic MTOC embedded in the nuclear membrane of the parasite (13). The SPMT network disassembles in stage V gametocytes, providing an increased deformability that is expected to permit transmigration across the endothelial barrier and exit from the bone marrow (27, 28).…”