Authors

D N Tagoe³; M K Gould¹; T Kalejaiye³; S Bachmaier¹; R J Burchmore³; D Horn²; M Boshart¹; H P De Koning³;  ¹ Ludwig-Maximillians-University of Munich, Germany;  ² University of Dundee;  ³ University of Glasgow

Discussion

cAMP plays an important role in the cell biology and the life cycle progression of Trypanosoma brucei. It is generated by a large number of adenylate cyclases, at least some of which appear to be constitutively active, and broken down by phosphodiesterases. Both classes of proteins have highly conserved active domains. However, almost nothing is known about how cAMP regulates key cellular functions including cytokinesis in cell division. Recently we reported on a set of proteins that appear to be involved in cAMP signalling in trypanosomes and named them cAMP Response Proteins (CARPs). Here, we focus on the role of CARP3 in cAMP signalling and regulation in T. brucei. Deleting CARP3 reduces sensitivity to the PDE inhibitor (CpdA) and increases both intracellular and extracellular cAMP levels. Conversely, overexpressing CARP3 sensitises the cells to CpdA. Co-immunoprecipitation revealed that CARP3 is associated with several adenylate cyclases, and CARP3 influenced adenylate cyclase expression in the presence of CpdA. These results validate a role for CARP3 as a regulator of adenylate cyclases in trypanosomes and as a key component of the cAMP signalling cascade.