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Eukaryotic Cell, January 2005, p. 147-155, Vol. 4, No. 1
1535-9778/05/$08.00+0     doi:10.1128/EC.4.1.147-155.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Homolog of Ste6, the a-Factor Transporter in Saccharomyces cerevisiae, Is Required for Mating but Not for Monokaryotic Fruiting in Cryptococcus neoformans

Yen-Ping Hsueh and Wei-Chiang Shen^*

Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan

Received 16 May 2004/ Accepted 13 October 2004

Fungal pheromones function during the initial recognition stage of the mating process. One type of peptide pheromone identified in ascomycetes and basidiomycetes terminates in a conserved CAAX motif and requires extensive posttranslational modifications to become mature and active. A well-studied representative is the a-factor of Saccharomyces cerevisiae. Unlike the typical secretory pathway utilized by most peptides, an alternative mechanism involving the ATP-binding cassette transporter Ste6 is used for the export of mature a-factor. Cryptococcus neoformans, a bipolar human pathogenic basidiomycete, produces CAAX motif-containing lipopeptide pheromones in both MATa and MAT cells. Virulence studies with a congenic pair of C. neoformans serotype D strains have shown that MAT cells are more virulent than MATa cells. Characterization of the MAT pheromones indicated that an autocrine signaling loop may contribute to the differentiation and virulence of MAT cells. To further address the role of pheromones in the signaling loop, we identified a STE6 homolog in the C. neoformans genome and determined its function by gene disruption. The ste6 mutants in either mating-type background showed partially impaired mating functions, and mating was completely abolished in a bilateral mutant cross. Surprisingly, the MAT ste6 mutant does not exhibit a defect in monokaryotic fruiting, suggesting that the activation of the autocrine signaling loop by the pheromone is via a Ste6-independent mechanism. MF pheromone itself is essential for this process and could induce the signaling response intracellularly in MAT cells. Our data demonstrate that Ste6 is evolutionarily conserved for mating and is not required for monokaryotic fruiting in C. neoformans.

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* Corresponding author. Mailing address: Department of Plant Pathology and Microbiology, Room 216, Building Number 1, National Taiwan University, No. 1 Roosevelt Rd., Sec. 4, 106 Taipei, Taiwan. Phone: 886-2-23630231-2733. Fax: 886-2-23636490. E-mail: wcshen{at}ntu.edu.tw.

Present address: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.

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Eukaryotic Cell, January 2005, p. 147-155, Vol. 4, No. 1
1535-9778/05/$08.00+0     doi:10.1128/EC.4.1.147-155.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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