In the Americas, from Mexico in the North to Argentina and Chile in the South, there are 18 to 20 million people infected with Trypanosoma cruzi, the causative agent of Chagas' disease. Estimated yearly incidence amounts to 561,000 cases not including countries like Argentina, Brazil, Chile and Uruguay where active programs of vector elimination have been in progress for years. It was estimated that 2 to 3 million individuals have the clinical symptoms that characterize the chronic stage of Chagas' disease, and that 45,000 of them die each year. Our long-term goal is to find targets for the treatment of Chagas' disease. While working in our project investigating the different Ca2+ compartments involved in the regulation of Ca2+ homeostasis in T. cruzi, we discovered a novel organelle, that we named the acidocalcisome because it is acidic and contains a large amount of releasable Ca 2+. We found recently that Ca2+ is stored in acidocalcisomes complexed with pyrophosphate and short chain polyphosphates. Drs. Cazzulo and Parodi, in addition, discovered the presence of calreticulin, a Ca2+ storage protein present in the endoplasmic reticulum of T. cruzi and described its involvement in glycoprotein synthesis. T. cruzi would have then two non-mitochondrial Ca2+ storage compartments with two different storage mechanisms: an acidic compartment in which Ca2+ is stored bound to polyphosphates (acidocalcisome), and a non-acidic compartment in which Ca2+ is stored bound to calreticulin and possibly other proteins (endoplasmic reticulum). T. cruzi constitutes then a unique model organism to study the relationship between acidic and non-acidic Ca2+ storage compartments in eukaryotic cells. We plan to collaborate in the elucidation of the role of calreticulin in Ca2+ homeostasis in these parasites.
Our specific aims are:
specific aim 1, to investigate the levels and location of calreticulin in T. cruzi different stages, and specific aim 2, to investigate the role of calreticulin in Ca2+ homeostasis in T. cruzi
