Signaling Pathways in Trypanosoma cruzi that Modulate Host Cell Interaction

Members of the Gp85/trans-sialidase (Gp85/TS) superfamily and mucins play an essential role in the invasion of host cells by T. cruzi trypomastigotes. Together, they constitute a large portion of the genome; approximately 700 and 433 genes encode Gp85/TS glycoproteins and mucins (as do a similar amount of pseudogenes), respectively. Gp85/TS proteins bind to a variety of host cell receptors and extracellular matrix components and binding of TS to host cells is independent of their enzymatic activity. Because mucins are the main substrate for TS, their interaction with host cells has been described as carbohydrate-dependent. Complex signaling cascades operate during the infection process within both parasite and host cells, but most research into signaling events has been limited to those of host cells. Much less information about the parasitic side is available; these pathways will be the subjects of intense research in the near future. Analyses of protein kinases and phosphatases in the parasite genome show pathways common to other organisms, but also parasite- specific pathways that should be exploited as candidates for drug targeting.