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Eukaryotic Cell, April 2002, p. 257-272, Vol. 1, No. 2
1535-9778/02/$04.00+0     DOI: 10.1128/EC.1.2.257-272.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mating-Type-Specific and Nonspecific PAK Kinases Play Shared and Divergent Roles in Cryptococcus neoformans

Ping Wang,1 Connie B. Nichols,1 Klaus B. Lengeler,1,2 Maria E. Cardenas,1 Gary M. Cox,1,3 John R. Perfect,1,3 and Joseph Heitman1,2,3,4*

Departments of Molecular Genetics and Microbiology,1 Medicine,3 Pharmacology and Cancer Biology,4 the Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 277102

Received 20 November 2001/ Accepted 22 January 2002

Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid MAT{alpha} and MATa cells. Virulence has been linked to the mating type, and MAT{alpha} cells are more virulent than congenic MATa cells. To study the link between the mating type and virulence, we functionally analyzed three genes encoding homologs of the p21-activated protein kinase family: STE20{alpha}, STE20a, and PAK1. In contrast to the STE20 genes that were previously shown to be in the mating-type locus, the PAK1 gene is unlinked to the mating type. The STE20{alpha}, STE20a, and PAK1 genes were disrupted in serotype A and D strains of C. neoformans, revealing central but distinct roles in mating, differentiation, cytokinesis, and virulence. ste20{alpha} pak1 and ste20a pak1 double mutants were synthetically lethal, indicating that these related kinases share an essential function. In summary, our studies identify an association between the STE20{alpha} gene, the MAT{alpha} locus, and virulence in a serotype A clinical isolate and provide evidence that PAK kinases function in a MAP kinase signaling cascade controlling the mating, differentiation, and virulence of this fungal pathogen.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, 322 CARL Building, Research Dr., Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu.

Eukaryotic Cell, April 2002, p. 257-272, Vol. 1, No. 2
1535-9778/02/$04.00+0     DOI: 10.1128/EC.1.2.257-272.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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