Role of the RAM network in cell polarity and hyphal morphogenesis in Candida albicans.
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.
Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Korea.
Yunkyoung
Y
Song
Seon Ah
SA
Cheon
Kyung Eun
KE
Lee
So-Yeon
SY
Lee
Byung-Kyu
BK
Lee
Doo-Byung
DB
Oh
Hyun Ah
HA
Kang
Jeong-Yoon
JY
Kim
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology*; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D025301:Hyphae / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D000935:Antifungal Agents; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; C430214:phocein