Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis

Abstract

The anaphase promoting complex/cyclosome (APC/C) is a highly conserved multi-subunit E3 ubiquitin ligase that controls mitotic division in eukaryotic cells by tagging cell cycle regulators for proteolysis. APC3 is a key component that contributes to APC/C function. Plasmodium, the causative agent of malaria, undergoes atypical mitotic division during its life cycle. Only a small subset of APC/C components has been identified in Plasmodium and their involvement in atypical cell division is not well understood. Here, using reverse genetics we examined the localisation and function of APC3 in Plasmodium berghei. APC3 was observed as a single focus that co-localised with the centriolar plaque during asexual cell division in schizonts, whereas it appeared as multiple foci in male gametocytes. Functional studies using gene disruption and conditional knockdown revealed essential roles of APC3 during these mitotic stages with loss resulting in a lack of chromosome condensation, abnormal cytokinesis and absence of microgamete formation. Overall, our data suggest that Plasmodium utilises unique cell cycle machinery to coordinate various processes during endomitosis, and this warrants further investigation in future studies.

Plasmodium bergheikinesin-5 associates with the spindle apparatus during cell division and is important for efficient production of infectious sporozoites

“…This cell division lacks several classical regulators such as polo-like kinases, group 1 cyclins and many components of the anaphase promoting complex [24][25][26][27]39]. The classical cell division kinase, cyclin dependent kinase 1 (CDK1) is not essential for cell division in Plasmodium [24], but the parasite does possess other divergent and apicomplexan specific kinases that may be important in this process [24,40].…”

“…Thus, Plasmodium has unusual ways to divide and survive under different physiological conditions in different hosts. As cell division in Plasmodium is atypical, so the molecules regulating cell division are also divergent from those of higher eukaryotes [24][25][26][27]. The large family of kinesins includes molecular motors that are essential for several processes during cell division [28,29], and in Plasmodium berghei there are nine kinesin genes, including two kinesin-8 genes that are important in cell division and male gamete formation [23,30].…”

Plasmodium berghei Kinesin-5 Associates With the Spindle Apparatus During Cell Division and Is Important for Efficient Production of Infectious Sporozoites

“…Asexual proliferation is by asynchronous closed mitosis to produce a multinucleate coenocyte that undergoes cytokinesis at the end of the cell cycle to produce haploid extracellular progeny. This cell division lacks several classical regulators such as polo-like kinases, group 1 cyclins and many components of the anaphase promoting complex ( Tewari et al., 2010 ; Solyakov et al., 2011 ; Guttery et al., 2014 ; Roques et al., 2015 ; Wall et al., 2018 ). The classical cell division kinase, cyclin dependent kinase 1 (CDK1) is not essential for cell division in Plasmodium ( Tewari et al., 2010 ), but the parasite does possess other divergent and apicomplexan specific kinases that may be important in this process ( Ward et al., 2004 ; Tewari et al., 2010 ; Fang et al., 2017 ).…”

“…Thus, Plasmodium has unusual ways to divide and survive under different physiological conditions in different hosts. As cell division in Plasmodium is atypical, so the molecules regulating cell division are also divergent from those of higher eukaryotes ( Tewari et al., 2010 ; Guttery et al., 2014 ; Roques et al., 2015 ; Wall et al., 2018 ). The large family of kinesins includes molecular motors that are essential for several processes during cell division ( Wordeman, 2010 ; Yount et al., 2015 ), and in Plasmodium berghei there are nine kinesin genes, including two kinesin-8 genes that are important in cell division and male gamete formation ( Zeeshan et al., 2019a ; Zeeshan et al., 2019b ).…”

Systematic analysis of Plasmodium myosins reveals differential expression, localisation, and function in invasive and proliferative parasite stages

“…Purified MyoE‐GFP schizonts were lysed and incubated with GFP‐Trap agarose beads (Chromotek) as described previously (Wall et al, ). The sample was then analysed by LC‐MS/MS.…”