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We investigated the role in cell morphogenesis and pathogenicity of the Candida albicans GPR1gene, encoding the G protein-coupled receptor Gpr1. Deletion of C. albicans GPR1has only minor effects in liquid hypha-inducing media but results in strong defects in the yeast-to-hypha transition on solid hypha-inducing media. Addition of cAMP, expression of a constitutively active allele of the Gα protein Gpa2 or of the catalytic protein kinase A subunit TPK1restores the wild-type phenotype of the CaGPR1-deleted strain. Overexpression of HST7, encoding a component of the mitogen-activated protein kinase pathway, does not suppress the defect in filamentation. These results indicate that CaGpr1 functions upstream in the cAMP–protein kinase A (PKA) pathway. We also show that, in the presence of glucose, CaGpr1 is important for amino acid-induced transition from yeast to hyphal cells. Finally, as opposed to previous reports, we show that CaGpa2 acts downstream of CaGpr1 as activator of the cAMP–PKA pathway but that deletion of neither CaGpr1 nor CaGpa2 affects glucose-induced cAMP signaling. In contrast, the latter is abolished in strains lacking CaCdc25 or CaRas1, suggesting that the CaCdc25-CaRas1 rather than the CaGpr1-CaGpa2 module mediates glucose-induced cAMP signaling in C. albicans.

We have investigated the role of 3',5'-cyclic-adenosine-monophosphate (cAMP) in mediating the coupling between energy metabolism and cell cycle progression in both synchronous cultures and oscillating continuous cultures of Saccharomyces cerevisiae. For the first time, a peak in intracellular cAMP was shown to precede the observed breakdown of trehalose and glycogen during cell cycle-related oscillations. Measurements in synchronous cultures demonstrated that this peak can be associated with the cell cycle dynamics of cAMP under conditions of glucose-limited growth, which was found to differ significantly from that observed in synchronous glucose-repressed cultures. Our results support the notion that cAMP plays a major role in mediating the integration of energy metabolism and cell cycle progression, both in the single cell and during cell cycle-related oscillations in continuous culture, respectively. Evidence is presented that the dynamic behaviour of intracellular cAMP during the cell cycle is modulated depending on nutrient supply. The implications of these findings regarding the role of cAMP in regulating cell cycle progression and energy metabolism are discussed. Copyright © 2003 John Wiley & Sons, Ltd.