Adenylate cyclases (ACs), much like guanylate cyclases (GCs), are increasingly recognized as essential parts of many plant processes including biotic and abiotic stress responses. In order to identify novel ACs, we have applied a search motif derived from experimentally tested GCs and identified a number of Arabidopsis thaliana candidates including a clathrin assembly protein (AT1G68110; AtClAP). AtClAP contains a catalytic centre that can complement the AC-deficient mutant cyaA in E. coli, and a recombinant AtClAP fragment (AtClAP^261–379) can produce cyclic adenosine 3′,5′ monophosphate (cAMP) from adenosine triphosphate (ATP) in vitro. Furthermore, an integrated analysis of gene expression and expression correlation implicate cAMP in pathogen defense and in actin cytoskeletal remodeling during endocytic internalization.

One strategy for improving responses and adaptation systems of plants to stress is to target molecules involved in signaling and transduction of the stimuli effected by stresses. One such molecule is adenylyl cyclase (AC) an enzyme that catalyzes the conversion of adenosine 5-triphosphate (ATP) to the second messenger, 3,5-cyclic adenosine monophosphate (cAMP). cAMP, in turn, transduces signals in response to the various biotic and abiotic stress factors. Surprisingly, as far as five decades ago, attempts to isolate ACs and/or detect cAMP from the research model plant, Arabidopsis thaliana, were inconclusive or a matter of serious debates due to the absence of appropriate techniques or advanced technologies. This chapter, therefore, herein takes the reader on a journey from the 1970s to the present day, unraveling the challenges encountered, developments made, and successes realized in efforts and attempts to identify and characterize ACs in A. thaliana. The chapter covers from the early age of unsuccessful attempts to the more recent and successful advanced technologies such as the motif search approach, omics analysis and homologous cloning. Perspectives on the direction that future knowledge-building around this important group of plant proteins are also shared.