A Saccharomyces cerevisiae G-protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose

In the yeast Saccharomyces cerevisiae the accumulation of cAMP is controlle d by an elaborate pathway. Only two triggers of the Has adenylate cyclase p athway are known. Intracellular acidification induces a Ras-mediated long-l asting cAMP increase. Addition of glucose to cells grown on a non-fermentab le carbon source or to stationary-phase cells triggers a transient burst in the intracellular cAMP level. This glucose-induced cAMP signal is dependen t on the Gi alpha-protein Gpa2. We show that the Gi-protein coupled recepto r (GPCR) Gpr1 interacts with Gpa2 and is required far stimulation of cAMP s ynthesis by glucose. Gpr1 displays sequence homology to GPCRs of higher org anisms. The absence of Gpr1 is rescued by the constitutively activated Gpa2 (Val-132) allele. In addition, we isolated a mutant allele of GPR1, named f il2, in a screen for mutants deficient in glucose-induced loss of heat resi stance, which is consistent with its lack of glucose-induced cAMP activatio n. Apparently, Gpr1 together with Gpa2 constitute a glucose-sensing system for activation of the cAMP pathway. Deletion of Gpr1 and/or Gpa2 affected c APK-controlled features (levels of trehalose, glycogen, heat resistance, ex pression of STRE-controlled genes and ribosomal protein genes) specifically during the transition to growth on glucose. Hence, an alternative glucose- sensing system must signal glucose availability for the Sch9-dependent path way during growth on glucose. This appears to be the first example of a GPC R system activated by a nutrient in eukaryotic cells. Hence, a subfamily of GPCRs might be involved in nutrient sensing.