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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Okagaki, LH; Wang, Y; Ballou, ER; O'Meara, TR; Bahn, Y-S; Alspaugh, JA; Xue, C; Nielsen, K

Published Date

  • October 2011

Published In

Volume / Issue

  • 10 / 10

Start / End Page

  • 1306 - 1316

PubMed ID

  • 21821718

Pubmed Central ID

  • 21821718

Electronic International Standard Serial Number (EISSN)

  • 1535-9786

Digital Object Identifier (DOI)

  • 10.1128/EC.05179-11


  • eng

Conference Location

  • United States