Sorting of Trypanosoma cruzi mucins and their role in invasion

CÁNEPA, GE; MESÍAS, AC; BUSCAGLIA CA

Guarujá, San Pablo

Congreso; 1st. International meeting on cell biology of pathogens; 2011

The American society of cell biology

* Background/Aims: The surface of the protozoan parasite Trypanosoma cruzi is covered with mucins, which contribute to parasite protection and host cell invasion. Tc mucins may be divided in two gene families based on sequence analysis and expression profile: those present in the insect stages (TcSMUG) and those present in the mammalian stages (TcMUC). In this study we employed a variety of techniques to examine the contribution of different structural motifs in the correct trafficking and processing of Tc mucins. The role of one particular TcMUC mucin, termed TSSA, in the process of host cell invasion was also addressed. * Methods: We combined genetic and biochemical approaches to develop a set of genetic constructs to assay the effect, and the interplay of, signal peptide and GPI anchor in the fate and post-translational modification of representative members of different Tc mucin families. To address the functional role of TSSA we carried out different cell binding and cell invasion assays in the presence of either recombinant constructs or antibodies against this molecule. * Results: Our major findings can be divided into two groups. Structural: i) Addition of the GPI moiety facilitates but it is not mandatory for mucin processing/secretion. ii) Glycosylation profile is dictated both by the pool of glycosyltransferases and by sequence determinants within each mucin. Functional: TSSA exhibits an adhesive capacity toward mammalian cell lines and, accordingly, inhibit parasite internalization when exogenously added. * Conclusion: The studies presented here allow us to get novel insights into T. cruzi mucin post-translational modification and trafficking. The involvement of TSSA in mediating mammalian cells recognition/invasion adds to the global picture of surfaceassociated glycoproteins as key players in host-pathogen biology.