title: The G protein-coupled receptor Gpr1 and the Galpha protein Gpa2 act through the cAMP-protein kinase A pathway to induce morphogenesis in Candida albicans.
abstract: We investigated the role in cell morphogenesis and pathogenicity of the Candida albicans GPR1 gene, encoding the G protein-coupled receptor Gpr1. Deletion of C. albicans GPR1 has 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 Galpha protein Gpa2 or of the catalytic protein kinase A subunit TPK1 restores 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.
authors.affiliation: Department of Molecular Microbiology, Flanders Interuniversity Institute for Biotechnology (VIB) and Laboratory of Molecular Cell Biology, Katholieke Universiteit Leuven, Flanders, Belgium.
authors.forename: Mykola M
authors.initials: MM
authors.lastname: Maidan
authors.forename: Larissa
authors.initials: L
authors.lastname: De Rop
authors.forename: Joke
authors.initials: J
authors.lastname: Serneels
authors.forename: Simone
authors.initials: S
authors.lastname: Exler
authors.forename: Steffen
authors.initials: S
authors.lastname: Rupp
authors.forename: Hélène
authors.initials: H
authors.lastname: Tournu
authors.forename: Johan M
authors.initials: JM
authors.lastname: Thevelein
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Dijck
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002176:Candida albicans / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D018797:Cell Cycle Proteins / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D025301:Hyphae / Q000378:metabolism; D008715:Methionine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011392:Proline / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014774:Virulence; D018631:ras Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D044385:GTP-Binding Protein alpha Subunits; D043562:Receptors, G-Protein-Coupled; D011392:Proline; D008715:Methionine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D018631:ras Proteins; D005947:Glucose