Building the Perfect Parasite: Cell Division in Apicomplexa
van Dooren GG (2007) Building the perfect
parasite: Cell division in Apicomplexa. PLoS Pathog 3(6): e78. doi:10.1371/journal.
ppat.0030078
Building the Perfect Parasite: Cell Division in Apicomplexa
Boris Striepen 0 1
Carly N. Jordan 0 1
Sarah Reiff 0 1
Giel G. van Dooren 0 1
0 Boris Striepen is with the Center for Tropical and Emerging Global Diseases and the Department of Cellular Biology, University of Georgia , Athens , Georgia , United States of America. Giel G. van Dooren is with the Center for Tropical and Emerging Global Diseases, University of Georgia , Athens , Georgia , United States of America. Carly N. Jordan and Sarah Reiff are with the Department of Cellular Biology, University of Georgia , Athens, Georgia , United States of America
1 Editor: B. Brett Finlay, University of British Columbia , Canada
A toxoplasmosis, and crytposporidiosis in humans, and picomplexans are pathogens responsible for malaria, 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.
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A wide variety of prokaryotic and eukaryotic pathogens
have evolved the ability to invade and replicate within the
cells of their hosts. Few have developed the level of
sophistication and control exerted by the members of the
Apicomplexa [1]. Upon contact with a suitable host cell,
apicomplexans can invade within seconds, with minimal
apparent disturbance of the infected cell (Figure 1). This
process is dependent on actin and myosin and is driven by
parasite and not host motility [2,3]. Tightly associated with
host cell penetration is the secretion of three distinct parasite
organelles: rhoptries, micronemes, and dense granules.
Secretion is timed in succession, and secreted proteins play
key roles in adhesion, motility and formation, and
elaboration of the parasitophorous vacuole, a new cellular
compartment established during invasion that the parasite
occupies during its intracellular development (see [4,5] for
detailed reviews of this process in Toxoplasma and Plasmodium,
respectively).
The cellular structure of the zoite, the non-replicative
extracellular stage, appears streamlined towards one goal:
finding and invading the next host cell. Zoites are found at
various stages of the apicomplexan life cycle and are the
product of asexual as well as sexual replication processes (see
Figure 1A for a simplified apicomplexan life cycle). The zoite
is highly polarized, with the apical tip containing the
organizing center for the subpellicular microtubles that run
along the longitudinal axis of the parasite [6]. This axis also
polarizes the cells motility, driving the parasite into host cells
with its apex first. In some species, the tip is further
elaborated by the conoid, a cytoskeletal structure that is built
from a unique, tightly wound tubulin polymer and is
extended during invasion and motility [7]. Importantly, the
apical end is also the site for rhoptry and microneme
secretion, with these organelles tightly packed into the
anterior portion of the cell. While the anterior of the zoite is
focused on invasion, the rest of cell carries the genetic
material and tools to grow and develop once in the host cell,
including a nucleus and a single mitochondrion, plastid, and
Golgi.
Divide and Conquer
While invasive zoites are similar across the phylum,
intracellular stages differ dramatically in size, shape, and
architecture (see Figure 2 for a selection of micrographs). The
basis for this diversity lies in the flexibility of the
apicomplexan cell cycle. Apicomplexans are able to dissociate
and variably mix and match three elements that follow each
other invariably in most other cells: DNA replication and
chromosome segregation, nuclear division, and, lastly,
cytokinesis or budding (see Figure 3 for a schematic). While
Toxoplasma completes (...truncated)