Building the Perfect Parasite: Cell Division in Apicomplexa

Abstract

Apicomplexans are pathogens responsible for malaria, toxoplasmosis, and crytposporidiosis in humans, and a wide range of livestock diseases. These unicellular eukaryotes are stealthy invaders, sheltering from the immune response in the cells of their hosts, while at the same time tapping into these cells as source of nutrients. The complexity and beauty of the structures formed during their intracellular development have made apicomplexans the darling of electron microscopists. Dramatic technological progress over the last decade has transformed apicomplexans into respectable genetic model organisms. Extensive genomic resources are now available for many apicomplexan species. At the same time, parasite transfection has enabled researchers to test the function of specific genes through reverse and forward genetic approaches with increasing sophistication. Transfection also introduced the use of fluorescent reporters, opening the field to dynamic real time microscopic observation. Parasite cell biologists have used these tools to take a fresh look at a classic problem: how do apicomplexans build the perfect invasion machine, the zoite, and how is this process fine-tuned to fit the specific niche of each pathogen in this ancient and very diverse group? This work has unearthed a treasure trove of novel structures and mechanisms that are the focus of this review.

GFP‐targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites

“…Cell division in apicomplexa and specifically how organelles are replicated and segregated into daughter parasites has been studied most thoroughly in Toxoplasma, with a recent study (Nishi et al, 2008) describing the morphology of the apicoplast, mitochondrion, nucleus, rhoptries, micronemes, endoplasmic reticulum, Golgi apparatus and inner membrane complex during cell division, and the temporal and spatial relationship between these organelles during the cell cycle. However, the mechanisms of cell division employed by Toxoplasma and Plasmodium parasites are different (Striepen et al, 2007), with Toxoplasma producing daughter parasites by endodyogeny and Plasmodium carrying out multiple rounds of nuclear division to become multinucleate (in erythrocytic or exo-erythrocytic schizogony), or to produce a polyploid nucleus (in sporogony within the oocyst) and then separately undergoing cytokinesis. How the apicoplast is divided in both Toxoplasma and Plasmodium spp.…”

Toxoplasma gondii sequesters centromeres to a specific nuclear region throughout the cell cycle

“…At the core of this flexibility is the budding mechanism by which Apicomplexa replicate. This complex process encompasses mitosis of the nucleus, assembly of the cytoskeletal and membrane elements that form the pellicle, loading of the growing bud with organelles, and finally emergence of fully formed new invasive daughters from the mother cell (2). Based on this underlying scheme, Apicomplexa have evolved three distinct cell-division types (Fig.…”

“…Based on these observations, we speculated that apicomplexan chromosomes remain permanently attached to the centrocone throughout the cell cycle and that this physical tethering provides a critical means to maintain genome integrity (2). We directly tested the tethering hypothesis by developing a marker to visualize the centromeres of apicomplexan chromosomes.…”

Emerging roles for protein S-palmitoylation in Toxoplasma biology

“…In Toxoplasma, the IMC is formed from patches of flattened sacs joined together by sutures, except for the apical cap, where only one truncated coneshaped plate is observed, and the posterior end where the IMC is interrupted (Dubremetz and Torpier, 1978). This unique organelle plays a structural role, contributing to the shape and robustness of the parasite, and acts as a scaffold for the growing daughter cells (Striepen et al, 2007). The IMC also serves as a platform for the anchoring of the molecular machinery, the glideosome, which powers parasite motility necessary for invasion of, and egress from, infected cells (Opitz and Soldati, 2002).…”