Biogenesis of and activities at the Toxoplasma gondii parasitophorous vacuole membrane. 2008

Anthony P Sinai
Department of Microbiology Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose St., Lexington, Kentucky 40536, USA. sinai@uky.edu

Apicomplexan parasites like Toxoplasma gondii are distinctive in their utilization of para site encoded motor systems to invade cells. Invasion results in the establishment of the parasitophorous vacuole (PV) within the infected cell. Most apicomplexans complete their intracellular tenure within the infected cell in the PV that is demarcated from the host cytoplasm by the parasitophorous vacuole membrane (PVM). In this chapter I focus on the events surrounding the formation of the PVM and selected activities attributed to it. Its central role as the interface between the parasite and its immediate environment, the host cytoplasm, is validated by the diversity of functions attributed to it. While functions in structural organization, nutrient acquisitions and signaling have been defined their molecular bases remain largely unknown. Several recent studies and the decoding of the Toxoplasma genome have set the stage for a rapid expansion in our understanding of the role of the PVM in parasite biology. Toxoplasma gondii, like all apicomplexan parasites are obligate intracellular pathogens. This family of parasites utilize their own actin-myosin based motor systems to gain entry into susceptible cells establishing themselves, in some cases transiently (e.g., Theileria spp) in specialized vacuolar compartment, the parasitophorous vacuole (PV). The T. gondii PV is highly dynamic compartment defining the replication permissive niche for the parasite. The delimiting membrane defining the parasitophorous vacuole, the parasitophorous vacuole membrane or PVM is increasingly being recognized as a specialized "organelle" that in the context of the infected cell is extracorporeal to the parent organism, the parasite. A systematic study of this enigmatic organelle has been severely limited by several issues. Primary among these is the fact that it is formed only in the context of the infected cell thereby limiting the amount of material. Secondly, unlike other cellular organelles that can often be purified by conventional approaches, the PVM, cannot be purified away from host cell organelles (see below). In spite of these significant obstacles considerable progress has been made in recent years toward understanding the biogenesis of the PVM, identification of its protein complement and the characterization of activities within it. These studies demonstrate that the PVM, on its own and by virtue of its interactions with cellular components, plays critical functions in the structural integrity of the vacuole, nutrient acquisition and the manipulation of cellular functions. In addition it appears that the repertoire of activities at the PVM is likely to be plastic reflecting temporal changes associated with the replicative phase of parasite growth. Finally, the PVM likely forms the foundation for the cyst wall as the parasite differentiates in the establishment of latent infection. As the critical border crossing between the parasite and invaded cell the study of the PVM provides a fertile area for new investigation aided by the recent decoding of the Toxoplasma genome (available at wwww.ToxoDB.org) and the application of proteomic analyses to basic questions in parasite biology.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D006790 Host-Parasite Interactions The relationship between an invertebrate and another organism (the host), one of which lives at the expense of the other. Traditionally excluded from definition of parasites are pathogenic BACTERIA; FUNGI; VIRUSES; and PLANTS; though they may live parasitically. Host-Parasite Relations,Parasite-Host Relations,Host-Parasite Relationship,Parasite-Host Interactions,Host Parasite Interactions,Host Parasite Relations,Host Parasite Relationship,Host-Parasite Interaction,Host-Parasite Relation,Host-Parasite Relationships,Interaction, Host-Parasite,Interaction, Parasite-Host,Interactions, Host-Parasite,Interactions, Parasite-Host,Parasite Host Interactions,Parasite Host Relations,Parasite-Host Interaction,Parasite-Host Relation,Relation, Host-Parasite,Relation, Parasite-Host,Relations, Host-Parasite,Relations, Parasite-Host,Relationship, Host-Parasite,Relationships, Host-Parasite
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014122 Toxoplasma A genus of protozoa parasitic to birds and mammals. T. gondii is one of the most common infectious pathogenic animal parasites of man. Toxoplasma gondii,Toxoplasma gondius,Toxoplasmas,gondius, Toxoplasma
D014617 Vacuoles Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. Vacuole
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal

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