title: Role of the Npr1 kinase in ammonium transport and signaling by the ammonium permease Mep2 in Candida albicans.
abstract: The ammonium permease Mep2 induces a switch from unicellular yeast to filamentous growth in response to nitrogen limitation in Saccharomyces cerevisiae and Candida albicans. In S. cerevisiae, the function of Mep2 and other ammonium permeases depends on the protein kinase Npr1. Mutants lacking NPR1 cannot grow on low concentrations of ammonium and do not filament under limiting nitrogen conditions. A G349C mutation in Mep2 renders the protein independent of Npr1 and results in increased ammonium transport and hyperfilamentous growth, suggesting that the signaling activity of Mep2 directly correlates with its ammonium transport activity. In this study, we investigated the role of Npr1 in ammonium transport and Mep2-mediated filamentation in C. albicans. We found that the two ammonium permeases Mep1 and Mep2 of C. albicans differ in their dependency on Npr1. While Mep1 could function well in the absence of the Npr1 kinase, ammonium transport by Mep2 was virtually abolished in npr1Δ mutants. However, the dependence of Mep2 activity on Npr1 was relieved at higher temperatures (37°C), and Mep2 could efficiently induce filamentous growth under limiting nitrogen conditions in npr1Δ mutants. Like in S. cerevisiae, mutation of the conserved glycine at position 343 in Mep2 of C. albicans to cysteine resulted in Npr1-independent ammonium uptake. In striking contrast, however, the mutation abolished the ability of Mep2 to induce filamentous growth both in the wild type and in npr1Δ mutants. Therefore, a mutation that improves ammonium transport by Mep2 under nonpermissible conditions eliminates its signaling activity in C. albicans.
authors.affiliation: Institut für Molekulare Infektionsbiologie, Universität Würzburg, Josef-Schneider-Strasse 2, Würzburg, Germany. joachim.morschhaeuser@mail.uni-wuerzburg.de
authors.forename: Benjamin
authors.initials: B
authors.lastname: Neuhäuser
authors.forename: Nico
authors.initials: N
authors.lastname: Dunkel
authors.forename: Somisetty V
authors.initials: SV
authors.lastname: Satheesh
authors.forename: Joachim
authors.initials: J
authors.lastname: Morschhäuser
mesh_terms: D001692:Biological Transport; D002176:Candida albicans / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D027682:Cation Transport Proteins; D005656:Fungal Proteins; D000644:Quaternary Ammonium Compounds; D011494:Protein Kinases