The Gp85 Surface Glycoproteins from Trypanosoma cruzi
Trypanosoma cruzi strains show distinctive characteristics as genetic polymorphism and infectivity. Large repertoires of molecules, such as the Gp85 glycoproteins, members of the Gp85/Trans-sialidase superfamily, as well as multiple signaling pathways, ar
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The Gp85 Surface Glycoproteins from Trypanosoma cruzi Eliciane C. Mattos, Renata R. Tonelli, Walter Colli, and Maria Julia M. Alves
Abstract Trypanosoma cruzi strains show distinctive characteristics as genetic polymorphism and infectivity. Large repertoires of molecules, such as the Gp85 glycoproteins, members of the Gp85/Trans-sialidase superfamily, as well as multiple signaling pathways, are associated with invasion of mammalian cells by the parasite. Due to the large number of expressed members, encoded by more than 700 genes, the research focused on this superfamily conserved sequences is discussed. Binding sites to laminin have been identified at the N-terminus of the Gp85 molecules. Interestingly, the T. cruzi protein phosphorylation profile is changed upon parasite binding to laminin (or fibronectin), particularly the cytoskeletal proteins such as those from the paraflagellar rod and the tubulins, which are both markedly dephosphorylated. Detailed analysis of the signaling cascades triggered upon T. cruzi binding to extracellular matrix (ECM) proteins revealed the involvement of the MAPK/ERK pathway in this event. At the C-terminus, the conserved FLY sequence is a cytokeratin-binding domain and is involved in augmented host cell invasion in vitro and high levels of parasitemia in vivo. FLY, which is associated to tissue tropism and preferentially binds to the heart vasculature may somehow be correlated with the severe cardiac form, an important clinical manifestation of chronic Chagas’ disease.
E.C. Mattos • W. Colli • M.J.M. Alves (*) Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, 05508-900 Cidade Universitária, São Paulo, Brazil e-mail: [email protected] R.R. Tonelli Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP, Brazil A.L.S. Santos et al. (eds.), Proteins and Proteomics of Leishmania and Trypanosoma, Subcellular Biochemistry 74, DOI 10.1007/978-94-007-7305-9_7, © Springer Science+Business Media Dordrecht 2014
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Abbreviations AEP Asp Box CK DGF DTU ECM ERK1/2 FAY motif FL-160 FLY motif FLY-phage FN FRIP motif Gal Galf GIPC GIPL GlcN Gp GPI H1A10 HBP IFN-γ IL-10 LPPG Man MAP MASP Mbp NO PD98059 PFR PI PIPLC PK PKAc PLD RGD motif RNAi SAPA Tc Tc80 POP
Aminoethylphosphonate SxDxGxTW amino acid sequence Cytokeratin Disperse gene family Discrete typing units Extracellular matrix Extracellular signal-regulated protein kinases 1 and 2 VTVxNVFAYNR amino acid sequence T. cruzi 160 kDa flagellum-associated protein VTVxNVFLYNR amino acid sequence Bacteriophages expressing the FLY motif Fibronectin xRxP amino acid sequence Galactose Galactofuranose Glycosylinositolphosphoceramide Glycoinositolphospholipid Glucosamine Glycoprotein Glycophosphatydilinositol mAb that recognizes members of the Tc85 glycoprotein family Heparin binding proteinase Interferon gamma Interleukin 10 Lipopeptidophosphoglycan Mannose Mitogen-activated protein Mucin-associated surface protein Mega base-pair Nitric oxi
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