Molecular Partitioning during Host Cell Penetration by <i>Toxoplasma gondii</i>

Charron, Audra J.; Sibley, L. David

doi:10.1111/j.1600-0854.2004.00228.x

Cited by 88 publications

(74 citation statements)

References 57 publications

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“…The selective exclusion of transmembrane proteins anchored in the cytoskeleton suggests that filtering takes place on the cytoplasmic face of the plasma membrane. Alternatively, many proteins appear to gain access to the vacuole by virtue of partitioning into lipid rafts [3,4]. This raises the intriguing possibility that the moving junction is a mechanism to order lipids within the bilayer and thus influence the protein composition of the vacuolar membrane.…”

Section: Defining the Moving Junctionmentioning

confidence: 99%

“…During invasion, the tight apposition of the host and parasite membranes forms a visible constriction known as the moving junction, which selectively restricts access of host proteins to the forming vacuole [3]. Most host cell membrane proteins are prevented from entering the forming vacuole by exclusion of transmembrane proteins with cytoplasmic tails and by a process that depends on protein partitioning in the lipid environment of the membrane [4]. This remarkable feat of invasion and vacuole remodeling takes a mere 15-20 seconds to complete, almost an order of magnitude faster than phagocytosis [2].…”

Section: Introductionmentioning

confidence: 99%

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Rhoptries: an arsenal of secreted virulence factors

Bradley

Sibley

2007

Current Opinion in Microbiology

174

136

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Apicomplexan parasites use actin-based motility coupled with regulated protein secretion from apical organelles to actively invade host cells. Critical in this process are rhoptries, club-shaped secretory organelles that discharge their contents during parasite invasion into host cells. A proteomic analysis of the rhoptries in Toxoplasma gondii demonstrated that this organelle contains a number of novel rhoptry proteins (ROP) including serine-threonine kinases and protein phosphatases. A subset of ROP proteins have been shown to target to the moving junction, which plays a key role in invasion and parasitophorous vacuole formation. Other ROP proteins have various destinations in the host cell including the host cell nucleus and the parasitophorous vacuole, likely reflecting their distinct targets and roles. Forward genetic analysis recently revealed that secretory ROP kinases dramatically influence host gene expression and are the major parasite virulence factors. Thus, ROP proteins are functionally analogous (although not homologous) to effectors released by type III and IV secretion systems, which are factors that play an important role in bacterial virulence. Deciphering the role of ROP effectors may allow specific disruption of these factors, thus offering new options for preventing disease.

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Section: Defining the Moving Junctionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rhoptries: an arsenal of secreted virulence factors

Bradley

Sibley

2007

Current Opinion in Microbiology

174

136

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“…MIC and rhoptry neck proteins (RON) assemble on the parasite surface to form the moving junction (MJ) [10], a tight apposition of the parasite and host plasma membranes visible during cell invasion. The moving junction ensures the formation of the parasitophorous vacuole membrane (PVM) from the host cell membrane while largely excluding host membrane proteins from the forming PVM [11]. This partitioning strategy procures a non-fusigenic state of the PVM with host structures, avoiding the potential acidification and destruction of the PV contents by fusion with host cell lysosomes [12].…”

Section: Introductionmentioning

confidence: 99%

Host cell manipulation by the human pathogen Toxoplasma gondii

Laliberté

Carruthers

2008

Cell. Mol. Life Sci.

158

123

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Toxoplasma gondii is an obligate intracellular parasite that can infect virtually any nucleated cell. During cell invasion Toxoplasma creates a subcellular compartment termed the parasitophorous vacuole, which acts as an interface between the parasite and host cytoplasm, and in many cases serves as a platform for modulation of several host cell functions that support parasite replication and infection. Spatial reorganization of host organelles and the remodeling of the cytoskeleton around the parasitophorous vacuole are observed early following entry and recent evidence suggests this interior redecorating promotes nutrient acquisition by the parasite. New findings also reveal that T. gondii manipulates signaling pathways of the host cell by deploying parasite kinases and a phosphatase, including at least two that infiltrate the host nucleus. T. gondii infection additionally controls several cellular pathways to establish an anti-apoptotic environment in a variety of cell types, and to subvert immune cells as a conduit for dissemination. In this review we discuss these recent developments in understanding how T. gondii achieves widespread success as a human and animal parasite by manipulating its host.

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“…This causes an invagination of the plasma membrane resulting in the formation of the parasitophorous vacuole (PV), which is the compartment that the parasite resides in throughout its time in the host cell. However, host plasma membrane-associated proteins are selectively incorporated into the developing PV such that glycosylphosphatidylinositol (GPI)-linked proteins are included, while single-pass transmembrane proteins are excluded (7,24).…”

mentioning

confidence: 99%

Host Cell Invasion by Toxoplasma gondii Is Temporally Regulated by the Host Microtubule Cytoskeleton

et al. 2010

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Toxoplasma gondii is an obligate intracellular protozoan parasite that invades and replicates within most nucleated cells of warm-blooded animals. The basis for this wide host cell tropism is unknown but could be because parasites invade host cells using distinct pathways and/or repertoires of host factors. Using synchronized parasite invasion assays, we found that host microtubule disruption significantly reduces parasite invasion into host cells early after stimulating parasite invasion but not at later time points. Host microtubules are specifically associated with the moving junction, which is the site of contact between the host cell and the invading parasite. Host microtubules are specifically associated with the moving junction of those parasites invading early after stimulating invasion but not with those invading later. Disruption of host microtubules has no effect on parasite contact, attachment, motility, or rate of penetration. Rather, host microtubules hasten the time before parasites commence invasion. This effect on parasite invasion is distinct from the role that host microtubules play in bacterial and viral infections, where they function to traffic the pathogen or pathogenderived material from the host cell's periphery to its interior. These data indicate that the host microtubule cytoskeleton is a structure used by Toxoplasma to rapidly infect its host cell and highlight a novel function for host microtubules in microbial pathogenesis.Toxoplasma gondii is an obligate intracellular protozoan parasite that is capable of causing disease in fetuses and immunocompromised individuals (23). The parasite infects a wide range of nucleated cells of most warm-blooded animals. The mechanisms underlying this wide tropism are not known but could be due to either the parasite infecting cells using a ubiquitously expressed host receptor and associated machinery, inserting its own receptor into the host cell's plasma membrane, or using multiple host cell receptors/machinery (5).Toxoplasma invasion is a multistep, complex process consisting of parasite contact to host cells, intimate attachment, parasite motility, and then penetration (5). Host cell contact is a loose, low-affinity interaction that is mediated by parasite surface antigens. An unknown signal then triggers the release of proteins from a specialized secretory organelle called micronemes whose contents include proteins that function as adhesins. This is then followed by parasite gliding motility on the host cell surface. At some point, proteins from a second secretory organelle, named rhoptries, are exocytosed. Among these rhoptry proteins, several (RON2, RON4, RON5, and RON8) are part of a preformed complex that binds the previously secreted AMA1 microneme protein (1,2,20,33). Together, these proteins form the moving junction complex, which defines the parasite entry site on the host cell plasma membrane. Parasite penetration occurs by the parasite propel-

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Molecular Partitioning during Host Cell Penetration by Toxoplasma gondii

Cited by 88 publications

References 57 publications

Rhoptries: an arsenal of secreted virulence factors

Rhoptries: an arsenal of secreted virulence factors

Host cell manipulation by the human pathogen Toxoplasma gondii

Host Cell Invasion by Toxoplasma gondii Is Temporally Regulated by the Host Microtubule Cytoskeleton

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