Heterologous Expression of a Trypanosoma cruzi Surface Glycoprotein (gp82) Indicates that Requirements for Glycosylphosphatidylinositol Anchoring are Different in Mammalian Cells and this Trypanosome

Ramirez, Marcel I.; Boscardin, Sílvia Beatriz; Ruiz, Rita C.; Han, Sang Won; Paranhos-Baccalà, Gláucia; Yoshida, Nobuko; Mortara, Renato Arruda; Silveira, José Franco da

doi:10.1590/s0074-02761999000400018

Cited by 3 publications

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“…Furthermore, this sequence is 85% identical to the previously described in MUC-R (a tagged version of a TcMUC gene), which rendered a GPI-anchored mucin when transfected into T. cruzi ( 19 ). Amino acid conservation included the critical tripeptide Asp-Gly-Ser, postulated to function as the ω, ω +1, and ω +2 positions for lipid attachment in GPI-anchored proteins from T. cruzi and Trypanosoma brucei ( 40 , 41 ). Two further evidences suggest that TSSA is GPI-anchored to the parasite surface.…”

Section: Discussionmentioning

confidence: 99%

A Trypanosoma cruzi Small Surface Molecule Provides the First Immunological Evidence that Chagas' Disease Is Due to a Single Parasite Lineage

Noia

Buscaglia

Marchi

et al. 2002

The Journal of Experimental Medicine

135

154

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Chagas' disease is a major health and economic problem caused by the protozoan Trypanosoma cruzi. Multiple independently evolving clones define a complex parasite population that can be arranged into two broad genetic lineages termed T. cruzi I and II. These lineages have different evolutionary origin and display distinct ecological and biological traits. Here we describe a novel molecule termed TSSA for trypomastigote small surface antigen that provides the first immunological marker allowing discrimination between lineages. TSSA is a surface, glycosylphosphatidyl inositol (GPI)-anchored mucin-like protein, highly antigenic during the infection. TSSA sequences from different parasite isolates reveal a population dimorphism that perfectly matches with the two T. cruzi lineages. Interestingly, this dimorphism is restricted to the central region of the molecule, which comprises the immunodominant B cell epitopes. This sequence variability has a major impact on TSSA antigenicity, leading to no immunological cross-reactivity between both isoforms for antibodies present either in immunization or infection sera. Furthermore, the absolute seroprevalence for TSSA in confirmed Chagasic patients is restricted to T. cruzi II isoform, strongly suggesting that human infections are due to this particular subgroup. Even though association of T. cruzi II with Chagas' disease has been proposed based on molecular markers, this is the first immunological evidence supporting this hypothesis. The implications of these results for the future research on Chagas' disease could be envisaged.

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Section: Discussionmentioning

confidence: 99%

A Trypanosoma cruzi Small Surface Molecule Provides the First Immunological Evidence that Chagas' Disease Is Due to a Single Parasite Lineage

Noia

Buscaglia

Marchi

et al. 2002

The Journal of Experimental Medicine

135

154

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“…Araya et al, 1994, [9] predicted the putative GP82 GPI-anchor cleavage/addition site based on the sequence of the clone J18. Similarly, Ramirez et al, 1999, [14, 46] analyzed in more detail the GPI-anchor signal of GP82 and other T. cruzi proteins and conducting homologous and heterologous expressions of GP82 in T. cruzi epimastigotes and mammalian cell systems. Despite the absence of a typical signal peptide in the protein encoded by the J18 clone, the authors found that T. cruzi machinery was able to translocate the protein inside the ER finally deliver it to the parasite's cell surface (Ramirez et al, 1999) [14].…”

Section: Synthesis and Processing Of Gp82mentioning

confidence: 99%

“…When the required signal was provided by insertion of the signal peptide from the influenza virus hemagglutinin, the mammalian cell was able to translocate the GP82 chimera inside the ER but proved insufficient to provide expression on the cell surface. These findings indicated that the requirements for GPI-anchoring are different between T. cruzi and mammalian cells [14, 46]. …”

Section: Synthesis and Processing Of Gp82mentioning

confidence: 99%

“…The putative GPI-anchor acceptor domain determined by Ramirez et al, 1999, [46] is formed by the amino acids aspartic ( ω ), glycine ( ω + 1), and serine ( ω + 2) (DGS) where the aspartic acid is linked to the GPI-anchor. A single mutation was introduced changing the aspartic acid to serine generating the sequence (SGS) which previously proved to be a feasible signal for GPI anchoring of T. brucei Variant Surface Glycoprotein (VSG) in mammals [48].…”

Section: Synthesis and Processing Of Gp82mentioning

confidence: 99%

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Genetic Structure and Expression of the Surface Glycoprotein GP82, the Main Adhesin of Trypanosoma cruzi Metacyclic Trypomastigotes

Corrêa

Cordero

Gentil

et al. 2013

The Scientific World Journal

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T. cruzi improves the likelihood of invading or adapting to the host through its capacity to present a large repertoire of surface molecules. The metacyclic stage-specific surface glycoprotein GP82 has been implicated in host cell invasion. GP82 is encoded by multiple genes from the trans-sialidase superfamily. GP82 shows a modular organization, with some variation of N-terminal region flanking a conserved central core where the binding sites to the mammalian cell and gastric mucin are located. The function of GP82 as adhesin in host cell invasion process could expose the protein to an intense conservative and selective pressure. GP82 is a GPI-anchored surface protein, synthesized as a 70 kDa precursor devoid of N-linked sugars. GPI-minus variants accumulate in the ER indicating that GPI anchor acts as a forward transport signal for progressing along the secretory pathway as suggested for T. cruzi mucins. It has been demonstrated that the expression of GP82 is constitutive and may be regulated at post-transcriptional level, for instance, at translational level and/or mRNA stabilization. GP82 mRNAs are mobilized to polysomes and consequently translated, but only in metacyclic trypomastigotes. Analysis of transgenic parasites indicates that the mechanism regulating GP82 expression involves multiple elements in the 3′UTR.

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Organization and expression of a multigene family encoding the surface glycoproteins of Trypanosoma cruzi metacyclic trypomastigotes involved in the cell invasion

Carmo

Araya

Ramirez

et al. 1999

Mem. Inst. Oswaldo Cruz

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Heterologous Expression of a Trypanosoma cruzi Surface Glycoprotein (gp82) Indicates that Requirements for Glycosylphosphatidylinositol Anchoring are Different in Mammalian Cells and this Trypanosome

Cited by 3 publications

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A Trypanosoma cruzi Small Surface Molecule Provides the First Immunological Evidence that Chagas' Disease Is Due to a Single Parasite Lineage

A Trypanosoma cruzi Small Surface Molecule Provides the First Immunological Evidence that Chagas' Disease Is Due to a Single Parasite Lineage

Genetic Structure and Expression of the Surface Glycoprotein GP82, the Main Adhesin of Trypanosoma cruzi Metacyclic Trypomastigotes

Organization and expression of a multigene family encoding the surface glycoproteins of Trypanosoma cruzi metacyclic trypomastigotes involved in the cell invasion

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