QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 9, 3768-3780, September 2006

This Article Full Text Full Text (PDF) All Versions of this Article: E06-02-0125v1 17/9/3768    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walton, F. J. Articles by Idnurm, A. Search for Related Content PubMed PubMed Citation Articles by Walton, F. J. Articles by Idnurm, A.

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

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

Submitted February 10, 2006; Revised May 16, 2006; Accepted June 7, 2006
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 Saccharomyces 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)

This article has been cited by other articles:

				A. Dunkler and J. Wendland Candida albicans Rho-Type GTPase-Encoding Genes Required for Polarized Cell Growth and Cell Separation Eukaryot. Cell, May 1, 2007; 6(5): 844 - 854. [Abstract] [Full Text] [PDF]