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Vol. 15, Issue 10, 4476-4489, October 2004

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PAK Kinases Ste20 and Pak1 Govern Cell Polarity at Different Stages of Mating in Cryptococcus neoformans

Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710

Submitted May 6, 2004; Revised July 14, 2004; Accepted July 15, 2004
Monitoring Editor: Peter Walter

Sexual identity and mating are linked to virulence of the fungal pathogen Cryptococcus neoformans. Cells of the mating type are more prevalent and can be more virulent than a cells, and basidiospores are thought to be the infectious propagule. Mating in C. neoformans involves cell-cell fusion and the generation of dikaryotic hyphae, processes that involve substantial changes in cell polarity. Two p21-activated kinase (PAK) kinases, Pak1 and Ste20, are required for both mating and virulence in C. neoformans. We show here that Ste20 and Pak1 play crucial roles in polarized morphogenesis at different steps during mating: Pak1 functions during cell fusion, whereas Ste20 fulfills a distinct morphogenic role and is required to maintain polarity in the heterokaryotic mating filament. In conclusion, our studies demonstrate that PAK kinases are necessary for polar growth during mating and that polarity establishment is necessary for mating and may contribute to virulence of C. neoformans.

^* Corresponding author. E-mail address: heitm001{at}duke.edu.

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