cAMP-Epac dependent regulation of T. cruzi invasion

MUSIKANT, D.; FERRI, G.; DURANTE IGNACIO; CARLOS ANDRES BUSCAGLIA; ALTSCHULER, D.; EDREIRA, M.

Woods Hole

Congreso; Molecular parasitology Meeting; 2014

?@ Chagas disease is a life-threatening illness caused by the protozoan parasite Trypanosoma cruzi and transmitted by blood-sucking triatomine insects from the Reduviidae family. cAMP has been shown to play critical roles in T. cruzi?fs cell cycle and host cell invasion. Mammalian host cell invasion by T. cruzi involves activation of host signaling pathways [1]. Attachment of infective stages of T. cruzi to the host cell is accompanied by elevation of intracellular cAMP levels in the host cell [2]. Parasite invasion involves the recruitment and fusion of lysosomes to the entry site [3], and it was shown that cAMP was able to potentiate the Ca2+-dependent exocytosis of lysosomes and lysosome-mediated cell invasion by T. cruzi [4]. However, the cAMP effectors involved are for the moment unknown. In mammalian cells, both cAMP effector pathways, i.e. PKA and Epac-Rap1, are involved in Ca2+ triggered exocytic events (i.e. secretion) [5]. Moreover, members of the pathway, including Rap1, were localized to late [6], and Epac-mediated Rap activation is involved in regulated exocytosis in human sperm [7], insulin secretion [20, 21] and pancreatic amylase release [22]. Our proposal focuses on the identification and characterization of new potential cAMP effectors in T. cruzi, and the dissection of mammalian host cAMP effector-pathways during T. cruzi invasion