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Vol. 19, Issue 12, 5456-5477, December 2008

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Role of the RAM Network in Cell Polarity and Hyphal Morphogenesis in Candida albicans

Yunkyoung Song^*, Seon Ah Cheon^*, Kyung Eun Lee^*, So-Yeon Lee^*, Byung-Kyu Lee, Doo-Byung Oh, Hyun Ah Kang, and Jeong-Yoon Kim^*

*Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Korea; Yuhan Research Institute, Gyeonggi-do 499-902, Korea; Korea Research Institute for Bioscience and Biotechnology, Daejeon 305-806, Korea; Department of Life Science, Chung-Ang University, Seoul 156-756, Korea

Submitted March 14, 2008; Revised September 15, 2008; Accepted September 25, 2008
Monitoring Editor: Charles Boone

RAM (regulation of Ace2p transcription factor and polarized morphogenesis) is a conserved signaling network that regulates polarized morphogenesis in yeast, worms, flies, and humans. To investigate the role of the RAM network in cell polarity and hyphal morphogenesis of Candida albicans, each of the C. albicans RAM genes (CaCBK1, CaMOB2, CaKIC1, CaPAG1, CaHYM1, and CaSOG2) was deleted. All C. albicans RAM mutants exhibited hypersensitivity to cell-wall- or membrane-perturbing agents, exhibiting cell-separation defects, a multinucleate phenotype and loss of cell polarity. Yeast two-hybrid and in vivo functional analyses of CaCbk1p and its activator, CaMob2p, the key factors in the RAM network, demonstrated that the direct interaction between the SMA domain of CaCbk1p and the Mob1/phocein domain of CaMob2p was necessary for hyphal growth of C. albicans. Genome-wide transcription profiling of a Camob2 mutant suggested that the RAM network played a role in serum- and antifungal azoles–induced activation of ergosterol biosynthesis genes, especially those involved in the late steps of ergosterol biosynthesis, and might be associated, at least indirectly, with the Tup1p-Nrg1p pathway. Collectively, these results demonstrate that the RAM network is critically required for hyphal growth as well as normal vegetative growth in C. albicans.

Address correspondence to: Jeong-Yoon Kim (jykim{at}cnu.ac.kr).