Chapter 189 - Cyclic Nucleotide Signaling in the Kinetoplastids

Abstract

This chapter provides a brief overview about cyclic nucleotide signaling in the kinetoplastids. The order of the kinetoplastida in the group of the Discicristates covers a vast empire of unicellular eukaryotes, many of which have adopted a parasitic lifestyle. They are characterized by an elongated cell body of 10–20 μM in length that is propelled by a single flagellum. Besides the cell nucleus, the kinetoplastids contain the name-giving kinetoplast, a specialized compartment of the mitochondrion that contains a mass of concantenated DNA circles, amounting to up to 10 percent of total cellular DNA. cAMP signaling in the kinetoplastids is starkly different from the pathways extensively studied in mammals. Importantly, kinetoplastid genomes do not code for G-protein-coupled receptors, or for heterotrimeric G proteins or protein kinase G. The kinetoplastid genomes all code for the same set of cyclic nucleotide-specific phosphodiesterases. There are no known downstream effectors of cAMP signaling identified in the kinetoplastids. Specifically, no cNMP-gated ion channels or Epacs were found in their genomes. Catalytic and regulatory subunits of protein kinase A are present, but their role in cAMP signaling remains unclear. The kinetoplastid genomes contain reasonably well conserved genes for catalytic and regulatory domains of protein kinase A. Numerous kinetoplastid proteins are predicted to contain cyclic nucleotide-binding domains. Compounds directed against components of cyclic nucleotide signaling pathways have long demonstrated their value in human pharmacology.