TcCARP3 modulates compartmentalized cAMP signals involved in osmoregulation, infection of mammalian cells, and colonization of the triatomine vector in the human pathogen Trypanosoma cruzi.

Abstract

Cyclic AMP signaling pathways are poorly understood in the stercorarian parasite Trypanosoma cruzi . Specifically, the mechanisms driving the activation of TcACs in response to microenvironmental stress are completely unknown. This study unveils the role of TcCARP3 in modulating the content of cAMP through the interaction with several TcACs and putative cAMP effectors in T. cruzi . Particularly, TcCARP3 interacts with TcAC1 in the main developmental stages of this parasite's life cycle, where both proteins display a dual localization pattern. These results provide new evidence supporting the compartmentalization of cAMP signals in trypanosomes. Moreover, our data unequivocally demonstrates that TcCARP3 is required for key cellular processes for parasite survival, such as response to osmotic stress, host cell invasion, intracellular replication, and the ability to colonize the hindgut of the triatomine vector. In summary, we found that TcCARP3 is an adenylate cyclase regulator, necessary for the life cycle progression of T. cruzi .