Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite

Abstract

Cytokinesis, or the division of the cytoplasm, following the end of mitosis or meiosis, is accomplished in animal cells, fungi, and amoebae, by the constriction of an actomyosin contractile ring, comprising filamentous actin, myosin II, and associated proteins. However, despite this being the best-studied mode of cytokinesis, it is restricted to the Opisthokonta and Amoebozoa, since members of other evolutionary supergroups lack myosin II and must, therefore, employ different mechanisms. In particular, parasitic protozoa, many of which cause significant morbidity and mortality in humans and animals as well as considerable economic losses, employ a wide diversity of mechanisms to divide, few, if any, of which involve myosin II. In some cases, cell division is not only myosin II-independent, but actin-independent too. Mechanisms employed range from primitive mechanical cell rupture (cytofission), to motility- and/or microtubule remodeling-dependent mechanisms, to budding involving the constriction of divergent contractile rings, to hijacking host cell division machinery, with some species able to utilize multiple mechanisms. Here, I review current knowledge of cytokinesis mechanisms and their molecular control in mammalian-infective parasitic protozoa from the Excavata, Alveolata, and Amoebozoa supergroups, highlighting their often-underappreciated diversity and complexity. Billions of people and animals across the world are at risk from these pathogens, for which vaccines and/or optimal treatments are often not available. Exploiting the divergent cell division machinery in these parasites may provide new avenues for the treatment of protozoal disease.

Alternate histories of cytokinesis: lessons from the trypanosomatids

“…Over the past few years, a series of proximity-dependent biotin identification (BioID), yeast two hybrid, and phosphoproteomic screens have been performed in an attempt to identify novel T. brucei cytokinetic regulators ( Hu et al , 2015 ; McAllaster et al , 2015 ; Hilton et al , 2018 ; Benz and Urbaniak, 2019 ). Detailed analyses of the identified proteins have recently been published elsewhere, so this discussion will be limited to a small subset ( Hammarton, 2019 ; Wheeler et al , 2019 ). The first proteomic screen was performed to identify TbPLK interactors and substrates.…”

Cytoskeletal diversification across 1 billion years: What red algae can teach us about the cytoskeleton, and vice versa

“…[60] Evidence from other eukaryotes about actin-less cytokinesis is more limited, but in organisms as diverse as Schizosaccharomyces pombe, Giardia, and Tetrahymena, actin filaments appears to be dispensable, at least for the later stages of furrow ingression. [62,79,80] How could cytokinesis occur without actin? Intriguingly, in the Pyropia yezoensis studies mentioned above, [41,55] the tip of the growing furrow appears connected to a "tubular vesicle" that has some resemblance to rough ER and might release early wall materials into the cell wall formed between daughter cells as ingrowth of the furrow occurs (Figure 3, panel a.3; see Ueki et al [41] for high magnification electron micrographs of the furrowing region).…”

“…So, how could furrowing cytokinesis (reviewed by [61]) happen in an organism that lacks myosin of any kind? The idea that furrowing cytokinesis involves myosin‐based contractility is deeply entrenched, but it has been called into question at least since the analysis of cytoplasmic division in myosin II null mutants in the slime mold Dictyostelium (see e.g., [62]). It has been proposed that actin filament depolymerization is sufficient to drive furrowing cytokinesis, which could potentially work if the filaments are dynamically cross‐linked.…”

Polo-like kinase in trypanosomes: an odd member out of the Polo family

“…Trypanosoma brucei, a flagellated unicellular protozoan and the causative agent of human sleeping sickness in sub-Saharan Africa, belongs to the Excavata supergroup of eukaryotes [13] and has a complex life cycle by alternating between the insect vector tsetse fly and the mammalian host. Trypanosoma brucei possesses many unusual features in cell cycle control [14][15][16][17][18]. Trypanosoma brucei has a closed mitosis and does not appear to assemble centrioles at the spindle poles during mitosis [19].…”