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Ras1 and Ras2 play antagonistic roles in regulating cellular cAMP level, stationary‐phase entry and stress response in Candida albicans
Author(s) -
Zhu Yong,
Fang HaoMing,
Wang YanMing,
Zeng GuiSheng,
Zheng XinDe,
Wang Yue
Publication year - 2009
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2009.06898.x
Subject(s) - biology , candida albicans , gtpase , mutant , saccharomyces cerevisiae , microbiology and biotechnology , hypha , yeast , biochemistry , gene
Summary The GTPase Ras1 activates the yeast‐to‐hypha transition in Candida albicans by activating cAMP synthesis. Here, we have characterized Ras2. Ras2 belongs to a group of atypical Ras proteins in some fungal species that share poor identity with other Ras GTPases with many variations in conserved motifs thought to be crucial for Ras‐associated activities. We find that recombinant Ras2 is enzymatically as active as Ras1. However, only RAS1 can rescue the lethality of the Saccharomyces cerevisiae ras1 ras2 mutant, suggesting functional divergence of the two genes. ras2 Δ is normal in hyphal growth, but deleting RAS2 in the ras1 Δ background greatly aggravates the hyphal defect, indicating that Ras2 also has a role in hyphal development. Strikingly, while RAS1 deletion causes a ∼20‐fold decrease in cellular cAMP, further deletion of RAS2 restores it to ∼30% of the wild‐type level. Consistently, while the ras1 Δ mutant enters the stationary phase prematurely, the double mutant does so normally. Moreover, ras1 Δ cells exhibit increased resistance to H 2 O 2 and higher sensitivity to the heavy metal Co 2+ , whereas ras2 Δ cells show the opposite phenotypes. Together, our data reveal a novel regulatory mechanism by which two antagonizing Ras GTPases balance each other in regulating multiple cellular processes in C. albicans .