Cited by 117Fungal Infections and StudiesFungal and yeast genetics researchAntifungal resistance and susceptibility

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

Open access
Okagaki, Laura H., Wang, Yina, Ballou, Elizabeth R., O'Meara, Teresa R., Bahn, Yong-Sun, Alspaugh, J. Andrew, Xue, Chaoyang, Nielsen, Kirsten·2011·Eukaryotic Cell

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 Ste3 a 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.

Integrity signals

Registry

Crossref · 10.1128/ec.05179-11

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Okagaki, L. H., Wang, Y., Ballou, E. R., O'Meara, T. R., Bahn, Y.-S., Alspaugh, J. A., Xue, C., & Nielsen, K.
Affiliations
  • University of Minnesota (US)
  • University of Medicine and Dentistry of New Jersey (US)
  • Duke University (US)
  • Department of Medicine, Duke University School of Medicine, Durham, North Carolina
  • Yonsei University (KR)
Corresponding author
Nielsen, Kirsten
Venue
Eukaryotic Cell
Published
2011-10
Volume
10
Issue
10
Pages
1306-1316
ISSN
  • 1535-9778 (ISSN-L)
  • 1535-9786
OpenAlex
W2104794604
Cited by
117
References
53
Citations by year
2026: 12 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 12 · 2021: 7 · 2020: 5 · 2019: 8 · 2018: 10 · 2017: 7 · 2016: 4 · 2015: 8 · 2014: 9 · 2013: 9 · 2012: 12
FWCI
8.19
Type
journal article
Language
en
Open access
Locations
  • Eukaryotic Cell (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1f33ai008027-01)
  • National Institute of Allergy and Infectious Diseases (R56AI074677, R01AI050128, AI089244, R01AI080275, AI08027, AI074677, AI070152, R01AI074677, U01AI089244, K22AI070152, AI050158)
Topics
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords
titan cells, Cryptococcus neoformans, G protein signaling, G protein-coupled receptors, GTPase-activating protein, GAP1, fungal virulence, pulmonary infection, cell wall thickening, ploidy, oxidative stress resistance
MeSH terms
Cyclic AMP, Animals, Cryptococcosis, Cryptococcus neoformans, Female, Fungal Proteins, Humans, Signal Transduction, Cyclic AMP-Dependent Protein Kinases, GTP-Binding Proteins, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review