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MBC in Press, published online ahead of print June 14, 2006
Mol. Biol. Cell 10.1091/mbc.E06-02-0125

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Submitted on February 10, 2006
Revised on May 16, 2006
Accepted on June 7, 2006

Conserved Elements of the RAM Signaling Pathway Establish Cell Polarity in the Basidiomycete Cryptococcus neoformans in a Divergent Fashion from Other Fungi

Felicia J. Walton, Joseph Heitman, and Alexander Idnurm

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710

Monitoring Editor: Charles Boone

In eukaryotes the complex processes of development, differentiation and proliferation require carefully orchestrated changes in cellular morphology. Single-celled eukaryotes provide tractable models for the elucidation of signaling pathways involved in morphogenesis. Here we describe a pathway regulating cell polarization and separation in the human pathogenic fungus Cryptococcus neoformans. An insertional mutagenesis screen identified roles for the ARF1, CAP60, NDH1, KIC1, CBK1, SOG2 and TAO3 genes in establishing normal colony morphology. ARF1 and CAP60 are also required for capsule production, a virulence factor, and ARF1 confers resistance to the antifungal fluconazole. KIC1, CBK1, SOG2 and TAO3 are homologues of genes conserved in other eukaryotes; in S. cerevisiae they constitute components of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. A targeted deletion of a fifth component of RAM (MOB2) conferred identical phenotypes to kic1, cbk1, sog2 or tao3 mutations. Characterization of these genes in C. neoformans revealed unique features of the RAM pathway in this organism. Loss of any of these genes caused constitutive hyperpolarization instead of the loss of polarity seen in S. cerevisiae. Furthermore, sensitivity to the drugs FK506 and cyclosporin A demonstrates that the RAM pathway acts in parallel with the protein phosphatase calcineurin in C. neoformans but not in S. cerevisiae. These results indicate that conserved signaling pathways serve both similar and divergent cellular roles in morphogenesis in these divergent organisms.

Address correspondence to: Joseph Heitman (heitm001{at}duke.edu) or Alexander Idnurm (idnur001{at}mc.duke.edu)




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A. Dunkler and J. Wendland
Candida albicans Rho-Type GTPase-Encoding Genes Required for Polarized Cell Growth and Cell Separation
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[Abstract] [Full Text] [PDF]


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