Vacuolar protein sorting mechanisms in apicomplexan parasites

Abstract

The phylum Apicomplexa comprises more than 5000 species including pathogens of clinical and economical importance. These obligate intracellular parasites possess a highly complex endomembrane system to build amongst others three morphologically distinct secretory organelles: rhoptries, micronemes and dense granules. Proteins released by these organelles are essential for invasion and hijacking of the host cell. Due to the complexity of the internal organization of these parasites, a wide panoply of trafficking factors was expected to be required for the correct sorting of proteins towards the various organelles. However, Toxoplasma gondii and other apicomplexan parasites contain only a core set of these factors and several of the vacuolar protein sorting (VPS) homologues found in most eukaryotes have been lost in this phylum.In this review, we will summarise our current knowledge about the role of trafficking complexes in T. gondii, highlighting recent studies focused on complexes formed by VPS proteins. We also present a novel, hypothetical model, suggesting the recycling of parasite membrane and micronemal proteins.

Wine glasses and hourglasses: Non-adaptive complexity of vesicle traffic in microbial eukaryotes

“…For comparison (Fig. 2E), we have shown the schematic traffic system of Toxoplasma gondii [8], [9], [10], [11], [12]. What immediately jumps out from these figures is the high degree of structure and visual complexity of the random cells, similar to that of a real vesicle traffic system.…”

“…By the same logic, compartment [011] “becomes” compartment [111]. This is the equivalent to the phenomenon of “compartmental maturation” seen in the progression of Golgi cisternae compositions [34], [35], [36], [37], the early-to-late endosome transition [38], and the maturation of precursor compartments to rhoptries in apicomplexans [8], [9], [10], [11], [12]. During maturation the compartment remains as an identifiable membrane-enclosed entity, but its composition changes over time.…”

“…The post-Golgi pathway is extensively modified in many organisms, especially parasites, adapted for secretion. For example, the rhoptries, micronemes and dense granules of the apicomplexans Toxoplasma and Plasmodium [8], [9], [10], [11], [12] are specialized secretory organelles essential for host cell invasion. Apart from the core secretory and endocytic pathways, these embellishments do not fit any simple formula: each new species presents new surprises.…”

Resolving the homology—function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology

“…These organisms possess a polarized endomembrane system including apical or “invasion” organelles, micronemes and rhoptries, to mediate host cell invasion and egress [25]. Apical organelles are likely divergent endo-lysosomes and other endo-lysosomal compartments, including an endosome-like compartment and vacuole, are also present, though the organization and identity of the endosomal system remains poorly understood [10,26,27]. …”

“…However, membrane trafficking is a central process underpinning growth, cell surface presentation and secretion. Thus it is critical to pathogenic mechanisms of many parasitic protists, for example by mediating host cell invasion [10] and immune system evasion [11]. It is therefore reasonable to ask what complement of membrane trafficking proteins is present across the broad diversity of eukaryotes and what we can infer about both evolution of the membrane trafficking system and the conserved set of eukaryotic membrane trafficking machinery, and how this has been modified in parasitic protists.…”