Role of a FYVE domain in a cAMP phosphodiesterase involved in osmoregulation in Trypanosoma cruzi.

SCHOIJET AC; DOCAMPO R; PIGNATARO OP; TORRES HN; FLAWIÁ MM; ALONSO GD

Puerto Madryn, Chubut.

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).

Intracellular levels of cyclic nucleotide second messengers are regulated predominantly by a large superfamily of phosphodiesterases (PDEs). Trypanosoma cruzi, the causative agent of Chagas disease, encodes four different PDE families. One of these PDEs, T. cruzi TcrPDEC2, has been previously characterized in our laboratory as a FYVE-domain containing protein. Here, we report a novel role for TcrPDEC2 in osmoregulation in T. cruzi and reveal the importance of its FYVE domain. Our data show that treatment of epimastigotes with TcrPDEC2 inhibitors stimulates the recovery of the parasites exposed to hyposmotic stress. In addition, TcrPDEC2 localizes to the contractile vacuole complex, a key organelle involved in osmoregulation. Furthermore, parasites overexpressing a truncated version of TcrPDEC2 without the FYVE domain show a failure in its subcellular localization and a marked decrease in PDE activity. Finally, we have previously characterized a phosphatidylinositol 3 kinase (TcVps34) in T. cruzi, which is also involved in osmorregulation and has been reported to interact with TcrPDEC2, and we are currently studying the role of TcVps15, a ser-thr protein kinase related to Vps34. Taking together, these results strengthen the importance of the cAMP signaling in T. cruzi and aim to reveal the network of the enzymes involved in the homeostasis in this parasite.