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MBC in Press, published online ahead of print January 26, 2005
Mol. Biol. Cell 10.1091/mbc.E04-09-0780

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Submitted on September 6, 2004
Revised on January 12, 2005
Accepted on January 13, 2005

The G Protein-coupled Receptor Gpr1 and the G{alpha} Protein Gpa2 Act through the cAMP-PKA Pathway to Induce Morphogenesis in Candida albicans

Mykola M. Maidan,*{dagger} Larissa De Rop,*{dagger} Joke Serneels,* Simone Exler,{ddagger} Steffen Rupp,{ddagger} Hélène Tournu,* Johan M. Thevelein,* and Patrick Van Dijck*

*Department of Molecular Microbiology, Flanders Interuniversity Institute for Biotechnology (VIB) and Laboratory of Molecular Cell Biology, Katholieke Universiteit Leuven, B-3001 Leuven-Heverlee, Flanders, Belgium; {ddagger}Fraunhofer IGB, 70569 Stuttgart, Germany

Monitoring Editor: Howard Riezman

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 G{alpha} 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 (MAPK) pathway, does not suppress the defect in filamentation. These results indicate that CaGpr1 functions upstream in the cAMP-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 completely 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.


{dagger}These authors contributed equally to this work.

Address correspondence to: E-mail: patrick.vandijck{at}bio.kuleuven.ac.be







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