Disease relevance of GPR1

• These findings suggest that Gpr1 and Gpa2 are involved in the glucose-sensing machinery that regulates morphogenesis and hypha formation in solid media via a cAMP-dependent mechanism, but they are not required for hypha formation in liquid medium or during invasive candidiasis [1].

High impact information on GPR1

• The G protein-coupled receptor Gpr1 and associated Galpha subunit Gpa2 govern dimorphic transitions in response to extracellular nutrients by signaling coordinately with Ras to activate adenylyl cyclase in the yeast Saccharomyces cerevisiae [2].
• In the yeast Saccharomyces cerevisiae, rapid activation of the cAMP pathway by glucose and sucrose requires the GPCR Gpr1 [3].
• Our results obtained by cysteine scanning mutagenesis and SCAM (substituted cysteine accessibility method) of residues in TMD VI provide strong evidence that glucose and sucrose directly interact as ligands with Gpr1 [3].
• These results are consistent with a model in which the GPR1/GPA2 pathway activates the Sch9p kinase to generate a response that acts in parallel with that generated by the Ras/cAMP pathway, resulting in the integration of nutrient signals [4].
• Filamentous growth is regulated by elements of the pheromone mitogen-activated protein (MAP) kinase cascade and a second signaling cascade involving the receptor Gpr1, the Galpha protein Gpa2, Ras2, and cyclic AMP (cAMP) [5].

Biological context of GPR1

• Here, we report that GPR1 encoding a putative G-protein-coupled receptor and GPA2 encoding a Galpha subunit are required for hypha formation and morphogenesis in C. albicans [1].
• We report here that the Gpr1 receptor is required for filamentous and haploid invasive growth and regulates expression of the cell surface flocculin Flo11 [6].
• We also show that GPR1 and GPA2 are required for a rapid increase in cell size in response to glucose [7].
• The glucose-induced higher cAMP level found in the strain with GPA2 in multicopy plasmid decreased by deletion of GPR1 gene [8].
• Gpr1 displays sequence homology to GPCRs of higher organisms [9].

Anatomical context of GPR1

• Strains of the yeast Saccharomyces cerevisiae, deficient in either of its two G-proteins, in the Snf3 and Rgt2 sensors, in the Gpr1 receptor and in various hexokinases were tested for their ability to start the activation cascade with a metabolizable monosaccharide that leads eventually to activation of plasma membrane H(+)-ATPase [10].

Associations of GPR1 with chemical compounds

• Because deletion of GPR1 or GPA2 reduces the glucose-induced cAMP increase the observed enhancement of Ras2 GTP loading is not sufficient for full stimulation of cAMP synthesis [11].
• Deletion of GPR1 slowed down adaptation to acetic acid, but had no effect on growth in the presence of acetic acid [12].
• The GPR1 gene encodes 961 amino acids with predicted seven transmembrane segments and two large cytosolic regions as third cytosolic loop with 350 amino acids where asparagine-rich region was found and the C-terminal region with 283 amino acids [13].
• The presence of the constitutively active Gpa2val132 allele in a wild-type strain bypassed the requirement for Gpr1 and increased the low cAMP signal induced by fructose and by low glucose up to the same intensity as the high glucose signal [14].
• Recently we have shown induction of Gpr1 internalization by specific amino acids, e.g. methionine [15].

Physical interactions of GPR1

• Recent studies have established a physical and functional link between the Galpha protein Gpa2 and the G protein-coupled receptor homolog Gpr1 [6].
• Phospholipase C binds to the receptor-like GPR1 protein and controls pseudohyphal differentiation in Saccharomyces cerevisiae [16].

Regulatory relationships of GPR1

• Epistasis analysis supports a model in which the Gpr1 receptor regulates pseudohyphal growth via the Gpa2p-cAMP-PKA pathway and independently of both the MAP kinase cascade and the PKA related kinase Sch9 [6].
• GPR1 regulates filamentous growth through FLO11 in yeast Saccharomyces cerevisiae [17].

Other interactions of GPR1

• GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p Galpha subunit and functions in a Ras-independent pathway [4].
• The Saccharomyces cerevisiae phospholipase C Plc1 is involved in cytosolic transient glucose-induced calcium increase, which also requires the Gpr1/Gpa2 receptor/G protein complex and glucose hexokinases [18].
• Among them, the gene ADY2/YCR010c was identified as a new key element for acetate transport, being homologous to the Yarrowia lipolytica GPR1 gene, which has a role in acetic acid sensitivity [19].

References