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Eukaryot Cell. 2011 Oct;10(10):1306-16. doi: 10.1128/EC.05179-11. Epub 2011 Aug 5.

Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli.

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1
Department of Microbiology, University of Minnesota, Minneapolis, MN, USA.

Abstract

The titan cell is a recently described morphological form of the pathogenic fungus Cryptococcus neoformans. Occurring during the earliest stages of lung infection, titan cells are 5 to 10 times larger than the normal yeast-like cells, thereby resisting engulfment by lung phagocytes and favoring the persistence of infection. These enlarged cells exhibit an altered capsule structure, a thickened cell wall, increased ploidy, and resistance to nitrosative and oxidative stresses. We demonstrate that two G-protein-coupled receptors are important for induction of the titan cell phenotype: the Ste3a pheromone receptor (in mating type a cells) and the Gpr5 protein. Both receptors control titan cell formation through elements of the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. This conserved signaling pathway, in turn, mediates its effect on titan cells through the PKA-regulated Rim101 transcription factor. Additional downstream effectors required for titan cell formation include the G(1) cyclin Pcl103, the Rho104 GTPase, and two GTPase-activating proteins, Gap1 and Cnc1560. These observations support developing models in which the PKA signaling pathway coordinately regulates many virulence-associated phenotypes in diverse human pathogens.

PMID:
21821718
PMCID:
PMC3187071
DOI:
10.1128/EC.05179-11
[Indexed for MEDLINE]
Free PMC Article
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