Protein Phosphatases in Trypanosome Growth and Development

In a eukaryotic cell, reversible phosphorylation regulates the functions of an estimated 30% of proteins, making this process one of the most common posttranslational modifications. The conformational changes of proteins due to phosphorylation are controlled by the dynamic interaction of protein phosphatases and kinases that constitute signaling pathways in unicellular and multicellular organisms. These signaling cascades control and coordinate a wide variety of intracellular and intercellular processes such as transcription, translation, cell cycle and cell division control, differentiation, motility, and cell-cell and cell-substrate interactions. Each of these processes contributes to the mechanisms that pathogens have evolved to survive in the hostile environment of their hosts and vectors. Consequently, these organisms have acquired a set of signaling molecules, including pathogen-specific kinases and phosphatases, that act within the pathogen itself or interact with the signaling pathways of the vector and the host. One of the most important - and evolutionarily ancient - groups of unicellular parasites is represented by the order of Trypanosomatida. Members of this order are flagellated unicellular organisms, and include extracellular and intracellular parasites responsible for severe diseases in humans and animals, mostly in tropical and subtropical regions of the world. In this chapter, attention will be focused on the protein phosphatases that have been characterized experimentally in the three most important trypanosomatids that infect humans, namely Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp.