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Eukaryot Cell

Title:		Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli
Author(s):		Okagaki LH; Wang Y; Ballou ER; O'Meara TR; Bahn YS; Alspaugh JA; Xue C; Nielsen K;
Address:		"Department of Microbiology, University of Minnesota, Minneapolis, MN, USA"
Journal Title:		Eukaryot Cell
Year:		2011
Volume:		20110805
Issue:		10
Page Number:		1306 - 1316
DOI:		10.1128/EC.05179-11
ISSN/ISBN:		1535-9786 (Electronic) 1535-9778 (Print) 1535-9786 (Linking)
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"
Keywords:		Animals Cryptococcosis/*microbiology Cryptococcus neoformans/*cytology/genetics/*metabolism Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/genetics/metabolism Female Fungal Proteins/genetics/*metabolism GTP-Binding Proteins/genetics/*metabolis;
Notes:		"MedlineOkagaki, Laura H Wang, Yina Ballou, Elizabeth R O'Meara, Teresa R Bahn, Yong-Sun Alspaugh, J Andrew Xue, Chaoyang Nielsen, Kirsten eng K22 AI070152-01A2/AI/NIAID NIH HHS/ AI050158/AI/NIAID NIH HHS/ R01 AI074677/AI/NIAID NIH HHS/ AI074677/AI/NIAID NIH HHS/ K22 AI070152/AI/NIAID NIH HHS/ K22 AI070152-02/AI/NIAID NIH HHS/ R01 AI080275/AI/NIAID NIH HHS/ AI089244/AI/NIAID NIH HHS/ AI070152/AI/NIAID NIH HHS/ AI08027/AI/NIAID NIH HHS/ R01 AI080275-02/AI/NIAID NIH HHS/ R56 AI074677/AI/NIAID NIH HHS/ R01 AI050128/AI/NIAID NIH HHS/ U01 AI089244/AI/NIAID NIH HHS/ R01 AI080275-01A2/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2011/08/09 Eukaryot Cell. 2011 Oct; 10(10):1306-16. doi: 10.1128/EC.05179-11. Epub 2011 Aug 5"