Role of Prokineticin receptors in Trypanosoma cruzi infection
Prokineticin receptor 1 and 2 (PKR1 and PKR2) are two G-protein coupled receptors (G-PCRs) which share 85% sequence identity, with the major differences concentrated in the amino and carboxyl-terminal regions of the molecules. Although both PKR1 and PKR2 are co-expressed in various tissues including brain, PKR1 is mainly expressed in peripheral tissues, while PKR2 is widely expressed in central nervous system. In rodents, prokineticin receptors (PKRs) are activated by small-secreted cysteine-rich peptides, prokineticin 1 and 2 (PK1 and PK2), and regulates a variety of biological processes including angiogenesis, neurogenesis, circadian rhythm, haematopoiesis, immune response or nociception.
Chagas disease is caused by the intracellular protozoan parasite Trypanosoma cruzi (T. cruzi) and infects >10 million people in Latin America. Although development of improved antiparasitic drugs is considered a priority, there have been no significant treatment advances in the past 40 years.
Recently, the GGIALAG sequence present in PKR2 was described as a new T. cruzi receptor for the Tc85 group of glycoproteins belonging to the gp85/TS superfamily and involved in cellular invasion of mammalian hosts.
Based on these considerations the project aims to analyse these host-parasite molecular complexes. Understanding the molecular details of how T. cruzi infects human's cells is an important step towards the development of new drugs for this disease.