2 CAMP RECEPTORS ACTIVATE COMMON SIGNALING PATHWAYS IN DICTYOSTELIUM

Multiple signal transduction pathways within a single cell may share c ommon components. In particular, seven different transmembrane helix r eceptors may activate identical pathways by interacting with the same G-proteins, Dictyostelium cells respond to cAMP using one such recepto r, cAR1, coupled by a typical heterotrimeric G-protein to intracellula r effecters. However, cells in which the gene for cAR1 has been delete d are unexpectedly still able to respond to cAMP. This implies either that certain responses are mediated by a different receptor than cAR1, or alternatively that a second, partially redundant receptor shares s ome of the functions of cAR1. We have examined the dose response and l igand specificity of one response, cAMP relay, and the dose response o f another, cyclic GMP synthesis. In each case, the EC(50) was similar to 100-fold higher and the maximal response was smaller in car1(-) tha n wild-type cells. These data indicate that cAR1 normally mediates res ponses to cAMP. The ligand specificity suggests that the responses see n in car1(-) mutants are mediated by a second receptor, cAR3. To test this hypothesis, we constructed a cell line containing deletions of bo th cAR1 and cAR3 genes. As predicted, these lines are totally insensit ive to cAMP. We conclude that the functions of the cAR1 and cAR3 recep tors are partially redundant and that both interact with the same hete rotrimeric G-protein to mediate these and other responses.