cAMP/Epac dependent regulation of T. cruzi invasion

DANIEL MUSIKANT, GABRIEL FERRI, IGNACIO DURANTE, CARLOS BUSCAGLIA, DANIEL L. ALTSCHULER, MARTIN M. EDREIRA

Woods Hole

Congreso; 2014 Molecular Parasitology Meeting; 2014

It has been shown that attachment of infective stages of T. cruzi to the host cell is accompanied by an increase of intracellular cAMP levels in the host and that the increased levels of cAMP were able to potentiate the Ca2+ dependent exocytosis of lysosomes and lysosome-mediated cell invasion by T. cruzi. In mammalian cells, both cAMP effector pathways, i.e. PKA and Epac-Rap1, are involved in Ca2+ triggered exocytic events. However, the cAMP effectors involved in the process of invasion by T. cruzi are for the moment unknown. Since Epac-mediated Rap activation is involved in regulated exocytosis in human sperm, insulin secretion and pancreatic amylase release, we hypothesized that the Epac-Rap1 cAMP pathway might play a functional role during T. cruzi invasion of the host cell. Using cAMP analogs to selectively activate/inhibit PKA or activate Epac in NRK cells, we shown that cAMP can induce invasion via specific activation of the Epac-mediated pathway. In contrast to the stimulatory effects Epac, PKA-dependent signaling had shown no effect on invasion. Moreover, data showed that PKA might be suppressing the effects of Epac when both pathways are simultaneously activated, suggesting a crosstalk between pathways in the regulation of invasion.