Cyclic AMP pathway and endocytic mechanisms in tripanosomatids.

TORRES, H.N.; SCHOIJET, A.C.; DOCAMPO, R.; FLAWIÁ, M.M.; ALONSO, G.

San Diego, California, USA

Congreso; Experimental Biology Annual Meeting; 2008

ASMBM

Several species of kinetoplastids cause major human infectious diseases. Trypanosoma cruzi is responsible of the fatal Chagas disease in South America, and Trypanosoma brucei is the agent of human sleeping sickness in Sub-Saharan Africa. In trypanosomatids, cAMP has been involved in the control of several processes such as proliferation, cell differentiation and osmoregulation. Recently, we have characterized two phosphodiesterases in T. cruzi: TcrPDEA1 and TcrPDEC2. TcrPDEC2 shows homology with PDE4 family and possess a N-terminal FYVE domain. This domain participate in vesicular trafficking by targeting proteins containing them to membranes enriched in PI 3-phosphate. After pre-incubation with specific type-4 PDE inhibitors, it was observed that parasites exposed to hypo-osmotic stress, showed an increase in the volume recovery. Moreover, TcrPDEC2 localized close to the contractile vacuole/flagellar pocket. We also characterize a putative class III PI 3-kinase. This enzyme, named TcVps34, is homologous to the S. cerevisiae Vps34p. By using PI3K inhibitors, it was observed that TcVps34 play a role in osmoregulation. In addition, epimastigotes over-expressing TcVps34, showed functional and large contractile vacuoles, defects in vesicular acidification and receptor-mediated endocytosis.