TgM2AP participates in <i>Toxoplasma gondii</i> invasion of host cells and is tightly associated with the adhesive protein TgMIC2

Rabenau, Karen E.; Sohrabi, Afshin; Tripathy, Ashutosh; Reitter, Christopher; Ajioka, James W.; Tomley, Fiona M.; Carruthers, Vern B.

doi:10.1046/j.1365-2958.2001.02513.x

Cited by 105 publications

(95 citation statements)

References 33 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MIC2 and M2AP form a 1:1 complex that does not contain any additional subunits, as demonstrated by metabolic labeling and quantitative immunoprecipitation (13). Our findings indicate that MIC2 and M2AP assemble into a complex of ϳ440 -460 kDa.…”

Section: Discussionsupporting

confidence: 54%

“…The majority of micronemal proteins characterized to date form complexes that are important for proper cellular trafficking and secretion (13,23,24,26). For example, soluble microneme proteins such as MIC1 and MIC4 require interaction with the membrane bound protein MIC6 to ensure proper targeting to the micronemes (24).…”

Section: Discussionmentioning

confidence: 99%

“…The MIC2 Protein Forms Multimeric Complexes-Protein complexes are implicated in the correct targeting of soluble microneme proteins (13,23,24). To test whether mut⌬C was capable of associating with endogenous MIC2, the full-length MIC2 protein was immunoprecipitated with antisera specific to the cytoplasmic domain.…”

Section: Fig 1 Mut⌬c Is Localized To the Micronemesmentioning

confidence: 99%

“…Recently, a Drosophila rhomboid protease was found to cleave a chimeric substrate containing the MIC2 transmembrane domain suggesting that a parasite-derived rhomboid might serve this function in vivo (11). A second micronemal protein, M2AP, is known to facilitate the transport of MIC2 through the secretory network (12,13). Mutant parasites that do not express M2AP (⌬m2ap) have a defect in parasite invasion presumably the consequence of insufficient transport of MIC2 to the micronemes (12).…”

mentioning

confidence: 99%

See 3 more Smart Citations

The Toxoplasma Proteins MIC2 and M2AP Form a Hexameric Complex Necessary for Intracellular Survival

Jewett

Sibley

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Toxoplasma gondii parasites gain entry into host cells through a process that depends on apically stored adhesins that are strategically released during invasion. One of these adhesins, microneme protein 2 (MIC2), is a type one transmembrane protein that binds to an accessory protein known as MIC2-associated protein (M2AP). Together the MIC2⅐M2AP complex participates in host cell attachment and invasion. The short cytoplasmic Cdomain of MIC2 is implicated in protein trafficking and mediating an association with the parasite cytoskeleton. To define the role of the cytoplasmic domain of MIC2, proteins lacking the C-domain were expressed in transgenic T. gondii. Surprisingly, protein trafficking and secretion were not affected. We hypothesized that mutant mic2 lacking the C-domain might be escorted to the micronemes by association with endogenous wild-type MIC2 possessing functional transmembrane and cytoplasmic domains. To investigate this interaction, native blue gels and gel filtration were employed to identify a stable macromolecular MIC2⅐M2AP complex of ϳ450 kDa. Our findings reveal that MIC2 and M2AP proteins form stable hexamers consisting of three ␣␤ dimers. Resolution of this complex has implications for how MIC2⅐M2AP associates with host cell receptors and the cytoskeleton to facilitate parasite motility and invasion.Apicomplexan parasites actively gain entry into host cells by a unique mechanism that depends on the cohesive interaction of cytoskeletal proteins and surface adhesins (1). Host cell invasion is fundamental to diseases caused by this phylum of pathogenic organisms that includes Plasmodium falciparum, the etiological agent of severe malaria and Toxoplasma gondii, the causative agent of toxoplasmosis. Tachyzoites (Toxoplasma) and sporozoites (Plasmodium) employ similar adhesins for active entry into host cells. These adhesins define a family of thrombospondin-related anonymous proteins (TRAPs) 1 (2, 3). TRAP family members are type 1 transmembrane proteins that are comprised of adhesive N-terminal domains that harbor integrin-like A-domains and at least one thrombospondin like domain and a short C-terminal cytoplasmic domain (C-domain) (2, 3). Toxoplasma gondii contains a single TRAP family member called MIC2, which is expressed by all of the invasive stages of the parasite. MIC2 is stored in the apically located microneme secretory organelles. Following host cell contact, microneme vesicles fuse with the proximal plasma membrane depositing MIC2 on the surface of the parasite (4 -6). Images of T. gondii captured at various stages of invasion indicate that MIC2 is translocated to the posterior end of the parasite during the rapid process of entry (7). Ultimately, MIC2 is removed from the parasite surface by a protease that cleaves the MIC2 protein within the transmembrane domain (8, 9). Amino acids within and just external to the transmembrane domain are implicated in this processing event (9, 10). Recently, a Drosophila rhomboid protease was found to cleave a chimeric substrate containing the M...

show abstract

Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Fig 1 Mut⌬c Is Localized To the Micronemesmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The Toxoplasma Proteins MIC2 and M2AP Form a Hexameric Complex Necessary for Intracellular Survival

Jewett

Sibley

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Three complexes have been described to date in T. gondii. TgMIC1/MIC4/MIC6 (Reiss et al, 2001) TgMIC3/MIC8 (Meissner et al, 2002a) and TgMIC2/M2AP (Rabenau et al, 2001) (Fig. 2A).…”

Section: Adhesinsmentioning

confidence: 87%

Molecular dissection of host cell invasion by the Apicomplexans: the glideosome

Soldati‐Favre

2008

Parasite

View full text Add to dashboard Cite

Summary :Gliding motility is an essential and fascinating apicomplexantypical adaptation to an intracellular lifestyle. Apicomplexan parasites rely on gliding motility for their migration across biological barriers and for host cell invasion and egress. This unusual substrate-dependent mode of locomotion involves the concerted action of secretory adhesins, a myosin motor, factors regulating actin dynamics and proteases. During invasion, complexes of soluble and transmembrane micronemes proteins (MICs) and rhoptry neck proteins (RONs) are discharged to the apical pole of the parasite, some protein acts as adhesins and bind to host cell receptors whereas others are involved in the moving junction formation. These complexes redistribute towards the posterior pole of the parasite via a physical connection to the parasite actomyosin system and are eventually released from the parasite surface by the action of parasite proteases.

show abstract

Global protein expression analysis in apicomplexan parasites: Current status

2005

View full text Add to dashboard Cite

Members of the phylum Apicomplexa are important protozoan parasites that cause some of the most serious, and in some cases, deadly diseases in humans and animals. They include species from the genus Plasmodium, Toxoplasma, Eimeria, Neospora, Cryptosporidium, Babesia and Theileria. The medical, veterinary and economic impact of these pathogens on a global scale is enormous. Although chemo- and immuno-prophylactic strategies are available to control some of these parasites, they are inadequate. Currently, there is an urgent need to design new vaccines or chemotherapeutics for apicomplexan diseases. High-throughput global protein expression analyses using gel or non-gel based protein separation technologies coupled with mass spectrometry and bioinformatics provide a means to identify new drug and vaccine targets in these pathogens. Protein identification based proteomic projects in apicomplexan parasites is currently underway, with the most significant progress made in the malaria parasite, Plasmodium falciparum. More recently, preliminary two-dimensional gel electrophoresis maps of Toxoplasma gondii and Neospora caninum tachyzoites and Eimeria tenella sporozoites, have been produced, as well as for micronemes in E. tenella. In this review, the status of proteomics in the analysis of global protein expression in apicomplexan parasites will be compared and the challenges associated with these investigations discussed.

show abstract

TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly associated with the adhesive protein TgMIC2

Cited by 105 publications

References 33 publications

The Toxoplasma Proteins MIC2 and M2AP Form a Hexameric Complex Necessary for Intracellular Survival

The Toxoplasma Proteins MIC2 and M2AP Form a Hexameric Complex Necessary for Intracellular Survival

Molecular dissection of host cell invasion by the Apicomplexans: the glideosome

Global protein expression analysis in apicomplexan parasites: Current status

Contact Info

Product

Resources

About