The ever unfolding story of cAMP signaling in trypanosomatids: vive la difference!

摘要: Kinetoplastids are unicellular, eukaryotic, flagellated protozoans containing the eponymous kinetoplast. Within this order, family of trypanosomatids responsible for some most serious human diseases, including Chagas disease (Trypanosoma cruzi), sleeping sickness brucei spp.), and leishmaniasis (Leishmania spp). Although cAMP is produced during life cycle stages these parasites, its signaling pathways very different from those mammals. The absence G-protein-coupled receptors, presence structurally adenylyl cyclases, paucity known effector proteins stringent need regulation in small kinetoplastid cells all suggest a significantly biochemical pathway likely cell biology. However, each main parasites express four class 1-type cyclic nucleotide-specific phosphodiesterases (PDEA-D), which have highly similar catalytic domains to that PDEs. To date, only TbrPDEB, expressed as two slightly isoforms TbrPDEB1 B2, has been found be essential when ablated. genomes contain reasonably well conserved genes regulatory protein kinase A, shown varied structural functional roles species. Recent discovery role cAMP/AMP metabolism quorum-sensing T. brucei, identification downstream Response Proteins (CARPs) whose expression levels correlate with sensitivity PDE inhibitors, suggests complex cascade. interplay between novel CARPs on division differentiation makes intriguing biology new paradigm signal transduction, potential targets trypanosomatid-specific pathway-based therapeutics.