Signal transduction under stress conditions in Trypanosoma cruzi

ALONSO, G.D.

San Miguel de Tucumán. Tucumán, Argentina.

Simposio; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2009

As Trypanosoma cruzi, the etiological agent of Chagas disease, passes through its complex life cycle, it comes across with different environmental stressors. One of the most relevant are the extreme fluctuations in osmolarity that occur within the gut of the vector, and also as the infective form passes out of the vector excreta (600-700 mOsm) and suddenly encounters the interstitial fluid of the mammalian host (300 mOsm). We have described a cAMP-specific phosphodiesterase, TcrPDEC2, which showed to be involved in osmoregulation. This enzyme depends on the presence of its FYVE domain, which is known to bind to membranes enriched in phosphatidylinositol 3-phosphate (PI 3-P), to be active. Moreover, TcrPDEC2 showed to be localized in the contractile vacuole complex (CVC), a key organelle involved in the release of water, and treatment with TcrPDEC2 inhibitors affects their capability to respond to hyposmotic stress. To determine if PI 3-P production might have a role in osmoregulation, we characterized TcVps34, the first phosphatidylinositol 3-kinase (PI3K) described in T. cruzi. TcVps34 specifically phosphorylates phosphatidylinositol to produce PI 3-P confirming that it belongs to class III PI3K family. Furthermore, in TcVps34-overexpressing parasites the localization of TcrPDEC2 showed to be altered, suggesting a possible role of TcVps34 determining TcrPDEC2 localization.