Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli

Laura H. Okagaki, Yina Wang, Elizabeth R. Ballou, Teresa R. O'Meara, Yong Sun Bahn, J. Andrew Alspaugh, Chaoyang Xue, Kirsten Nielsen

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1306-1316
Number of pages11
JournalEukaryotic Cell
Volume10
Issue number10
DOIs
Publication statusPublished - 2011 Oct 1

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Saturn
GTP-Binding Proteins
Cyclic AMP-Dependent Protein Kinases
Cyclin G
Pheromone Receptors
Phenotype
GTPase-Activating Proteins
Adenylate Kinase
Lung
Cryptococcus neoformans
Ploidies
GTP Phosphohydrolases
Phagocytes
G-Protein-Coupled Receptors
Infection
Cyclic AMP
Cell Wall
Capsules
Virulence
Oxidative Stress

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

Okagaki, L. H., Wang, Y., Ballou, E. R., O'Meara, T. R., Bahn, Y. S., Alspaugh, J. A., ... Nielsen, K. (2011). Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli Eukaryotic Cell, 10(10), 1306-1316. https://doi.org/10.1128/EC.05179-11
Okagaki, Laura H. ; Wang, Yina ; Ballou, Elizabeth R. ; O'Meara, Teresa R. ; Bahn, Yong Sun ; Alspaugh, J. Andrew ; Xue, Chaoyang ; Nielsen, Kirsten. / Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli In: Eukaryotic Cell. 2011 ; Vol. 10, No. 10. pp. 1306-1316.
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Okagaki, LH, Wang, Y, Ballou, ER, O'Meara, TR, Bahn, YS, Alspaugh, JA, Xue, C & Nielsen, K 2011, 'Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli ', Eukaryotic Cell, vol. 10, no. 10, pp. 1306-1316. https://doi.org/10.1128/EC.05179-11

Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli . / Okagaki, Laura H.; Wang, Yina; Ballou, Elizabeth R.; O'Meara, Teresa R.; Bahn, Yong Sun; Alspaugh, J. Andrew; Xue, Chaoyang; Nielsen, Kirsten.

In: Eukaryotic Cell, Vol. 10, No. 10, 01.10.2011, p. 1306-1316.

Research output: Contribution to journalArticle

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