The T. cruzi trans-sialidase induces PC12 cell differentiation via MAPK/ERK pathway

The trans-sialidase (TS) of Trypanosoma cruzi induces survival and differentiation of neuronal and glial cells. This mechanism underlying survival is via phosphatidylinositol 3-kinase (PI3K) but how TS promotes neuronal differentiation remained to be determined. Here we show that TS-induced neurite outgrowth in PC12 cells is through sustained activation of the mitogen-activated protein kinase or ERK cascade and, therefore, by a signaling mechanism distinct from the one it uses to induce cell survival. Such differential activation of signal pathways in neuronal cells to effectuate diverse biological activities is analogous to the action of authentic neurotrophins and other growth factors, thereby reinforcing the novel concept of T. cruzi mimicry of host neurotrophic factor(s).