gp63 homologues in Trypanosoma cruzi: surface antigens with metalloprotease activity and a possible role in host cell infection.
gp63 is a highly abundant glycosylphosphatidylinositol (GPI)-anchored membrane protein expressed predominantly in the promastigote but also in the amastigote stage of Leishmania species. In Leishmania spp., gp63 has been implicated in a number of steps in establishment of infection. Here we demonstrate that Trypanosoma cruzi, the etiological agent of Chagas' disease, has a family of gp63 genes composed of multiple groups. Two of these groups, Tcgp63-I and -II, are present as high-copy-number genes. The genomic organization and mRNA expression pattern were specific for each group. Tcgp63-I was widely expressed, while the Tcgp63-II group was scarcely detected in Northern blots, even though it is well represented in the T. cruzi genome. Western blots using sera directed against a synthetic peptide indicated that the Tcgp63-I group produced proteins of approximately 78 kDa, differentially expressed during the life cycle. Immunofluorescence staining and phosphatidylinositol-specific phospholipase C digestion confirmed that Tcgp63-I group members are surface proteins bound to the membrane by a GPI anchor. We also demonstrate the presence of metalloprotease activity which is attributable, at least in part, to Tcgp63-I group. Since antibodies against Tcgp63-I partially blocked infection of Vero cells by trypomastigotes, a possible role for this group in infection is suggested.
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D001483:Base Sequence; D002522:Chlorocebus aethiops; D016054:DNA, Protozoan / Q000235:genetics; D017125:Genes, Protozoan; D007891:Leishmania / Q000235:genetics / Q000276:immunology; D008666:Metalloendopeptidases / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D014709:Vero Cells; D014774:Virulence
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania