How cells monitor the availability of nutrition and transduce signals is a fundamental, unanswered question. We have found that Gpr1p, a recently identified G-protein (Gpa2p) coupled receptor in yeast Saccharomyces cerevisiae, regulate the cellular cAMP level in response to glucose. The glucose-induced higher cAMP level found in the strain with GPA2 in multicopy plasmid decreased by deletion of GPR1 gene. A transient increase of cAMP in response to glucose was not observed in a Deltagpr1 mutant strain and this defect was complemented and restored by introducing GPR1 gene with YCp vector. Gpr1p was also required for the increase of cAMP in response to other fermentable sugars. Both membrane proximal regions o the third cytosolic loop in Gpr1p, which has been shown to be important for coupling to G-proteins, were also required for glucose-induced transient increase of cAMP. Our findings suggest that Gpr1p is part of the nutrition sensing machinery most likely acting as a receptor to monitor glucose as well as other fermentable sugars and regulate cellular cAMP levels.
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