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PMID: 14871933 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans.

Eukaryotic cell ·Vol. 3 ·No. 1 ·2004-02-00 ·Pages 14-26

Hicks JK, D'Souza CA, Cox GM, Heitman J

Abstract

Our earlier findings established that cyclic AMP-dependent protein kinase functions in a signaling cascade that regulates mating and virulence of Cryptococcus neoformans var. grubii (serotype A). Mutants lacking the serotype A protein kinase A (PKA) catalytic subunit Pka1 are unable to mate, fail to produce melanin or capsule, and are avirulent in animal models, whereas mutants lacking the PKA regulatory subunit Pkr1 overproduce capsule and are hypervirulent. Because other mutations have been observed to confer different phenotypes in two diverged varieties of C. neoformans (grubii variety [serotype A] and neoformans variety [serotype D]), we analyzed the functions of the PKA genes in the serotype D neoformans variety. Surprisingly, the Pka1 catalytic subunit was not required for mating, haploid fruiting, or melanin or capsule production of serotype D strains. Here we identify a second PKA catalytic subunit gene, PKA2, that is present in both serotype A and D strains of C. neoformans. The divergent Pka2 catalytic subunit was found to regulate mating, haploid fruiting, and virulence factor production in serotype D strains. In contrast, Pka2 has no role in mating, melanin production, or capsule formation in serotype A strains. Our studies illustrate how different components of signaling pathways can be co-opted and functionally specialized during the evolution of related but distinct varieties or subspecies of a human fungal pathogen.

MeSH Terms
Alleles Amino Acid Sequence Animals Catalytic Domain Cell Nucleus/metabolism Cryptococcosis/microbiology Cryptococcus neoformans/metabolism Cyclic AMP-Dependent Protein Kinases/chemistry,metabolism Gene Deletion Genotype Haploidy Laccase/metabolism Melanins/biosynthesis Mice Mice, Inbred DBA Microscopy, Confocal Molecular Sequence Data Mutation Phenotype Phylogeny Plasmids/metabolism Polymerase Chain Reaction Protein Isoforms Protein Structure, Tertiary Saccharomyces cerevisiae/metabolism Sequence Homology, Amino Acid Signal Transduction Time Factors Virulence Factors/metabolism
Chemicals
Melanins Protein Isoforms Virulence Factors Laccase Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hicks Julie K
Department of Molecular Genetics and Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
D'Souza Cletus A
Cox Gary M
Heitman Joseph
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Article Info
Journal
Eukaryotic cell
Abbr.
Eukaryot Cell
ISSN
1535-9778
DOI
10.1128/EC.3.1.14-26.2004
Published
2004-02-00
Pages
14-26
Language
English
Region
United States
NLM ID
101130731
PMCID
PMC329511
Subset
IM
Grants
NIAID NIH HHS · R37 AI039115 · United States
NIAID NIH HHS · R01 AI042159 · United States
NIAID NIH HHS · R01 AI42159 · United States
NIAID NIH HHS · R01 AI039115 · United States
NIAID NIH HHS · R01 AI39115 · United States
NIAID NIH HHS · P01 AI44975 · United States
NIAID NIH HHS · P01 AI044975 · United States
External Links
PubMed source DOI: 10.1128/EC.3.1.14-26.2004 PMC Full Text View journal details
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