The G-Protein beta  Subunit GPB1 Is Required for Mating and Haploid Fruiting in Cryptococcus neoformans

doi:10.1128/MCB.20.1.352-362.2000

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Molecular and Cellular Biology, January 2000, p. 352-362, Vol. 20, No. 1
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The G-Protein $beta$ Subunit GPB1 Is Required for Mating and Haploid Fruiting in Cryptococcus neoformans

Ping Wang,¹ John R. Perfect,²^,³ and Joseph Heitman¹^,²^,³^,⁴^,⁵^,^*

Departments of Genetics,¹ Medicine,² Microbiology,³ and Pharmacology and Cancer Biology⁴ and Howard Hughes Medical Institute,⁵ Duke University Medical Center, Durham, North Carolina 27710

Received 16 June 1999/Returned for modification 27 July 1999/Accepted 4 October 1999

Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle. The gene encoding a heterotrimericG-protein $beta$ subunit, GPB1, was cloned and disrupted. gpb1 mutantstrains are sterile, indicating a role for this gene in mating.GPB1 plays an active role in mediating responses to pheromonesin early mating steps (conjugation tube formation and cell fusion)and signals via a mitogen-activated protein (MAP) kinase cascadein both MAT $alpha$ and MATa cells. The functions of GPB1 are distinctfrom those of the G $alpha$ protein GPA1, which functions in a nutrient-sensingcyclic AMP (cAMP) pathway required for mating, virulence factorinduction, and virulence. gpb1 mutant strains are also defectivein monokaryotic fruiting in response to nitrogen starvation. Weshow that MATa cells stimulate monokaryotic fruiting of MAT $alpha$ cells,possibly in response to mating pheromone, which may serve to dispersecells and spores to locate mating partners. In summary, the G $beta$ subunit GPB1 and the G $alpha$ subunit GPA1 function in distinct signalingpathways: one (GPB1) senses pheromones and regulates mating andhaploid fruiting via a MAP kinase cascade, and the other (GPA1)senses nutrients and regulates mating, virulence factors, andpathogenicity via a cAMPcascade.

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

Molecular and Cellular Biology, January 2000, p. 352-362, Vol. 20, No. 1
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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The G-Protein Subunit GPB1 Is Required for Mating and Haploid Fruiting in Cryptococcus neoformans

The G-Protein $beta$ Subunit GPB1 Is Required for Mating and Haploid Fruiting in Cryptococcus neoformans