Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans

Cruz, M.Cristina; Fox, Deborah S.; Heitman, Joseph

doi:10.1093/emboj/20.5.1020

Cited by 150Fungal Infections and StudiesFungal and yeast genetics researchSignaling Pathways in Disease

Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans

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Cruz, M.Cristina, Fox, Deborah S., Heitman, Joseph·2001·The EMBO Journal

DOI 10.1093/emboj/20.5.1020PMC PMC145507

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Abstract

Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised patients. Its growth is sensitive to the immunosuppressants FK506 and cyclosporin, which inhibit the Ca2+- calmodulin-activated protein phosphatase calcineurin. Calcineurin is required for growth at 37 degrees C and virulence of C.neoformans. We found that calcineurin is also required for mating. FK506 blocks mating of C.neoformans via FKBP12-dependent inhibition of calcineurin, and mutants lacking calcineurin are bilaterally sterile. Calcineurin is not essential for the initial fusion event, but is required for hyphal elongation and survival of the heterokaryon produced by cell fusion. It is also required for hyphal elongation in diploid strains and during asexual haploid fruiting of MATalpha cells in response to nitrogen limitation. Because mating and haploid fruiting produce infectious basidiospores, our studies suggest a second link between calcineurin and virulence of C.neoformans. Calcine urin regulates filamentation and 37 degrees C growth via distinct pathways. Together with studies revealing that calcineurin mediates neurite extension and neutrophil migration in mammals, our findings indicate that calcineurin plays a conserved role in the control of cell morphology.

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In C. neoformans, calcineurin governs both morphogenesis during sexual reproduction and growth at host temperature.
“In C. neoformans, calcineurin governs both morphogenesis during sexual reproduction and growth at host temperature (Odom et al. 1997; Cruz et al. 2001).”
From Genetic analysis of Hsp90 function in Cryptococcus neoformans highlights key roles in stress tolerance and virulence (2022) · cites this paper as Cruz et al. 2001
In C. neoformans, calcineurin is required for hyphal elongation during mating, cell fusion and asexual haploid fruiting of MATα cells in response to nitrogen limitation.
“In C. neoformans, calcineurin is required for hyphal elongation during mating, cell fusion and asexual haploid fruiting of MATα cells in response to nitrogen limitation (Cruz et al., 2001).”
From Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis (2014) · cites this paper as Cruz et al., 2001

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Authors: Cruz, M. C., Fox, D. S., & Heitman, J.
Affiliations: Howard Hughes Medical Institute (US)
Duke University (US)
Corresponding author: Heitman, Joseph
ORCID: Heitman, Joseph
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2001-03-01
Volume: 20
Issue: 5
Pages: 1020-1032
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1093/emboj/20.5.1020
PMC: PMC145507
OpenAlex: W2148376015
Cited by: 150
References: 90
Citations by year: 2025: 2 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 10 · 2016: 5 · 2015: 6 · 2014: 14 · 2013: 5 · 2012: 5
FWCI: 5.60
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health (5r01ai041937-03)
U.S. Public Health Service (A139115)
National Institute of Allergy and Infectious Diseases (P01-AI44975, R01AI042159, P01AI044975, AI42159, T32 AI07391-10, AI-44975, AI41937-S1, T32AI007392)
Topics: Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: calcineurin, Cryptococcus neoformans, hyphal elongation, mating, FK506, cyclosporine, FKBP12, heterokaryons, filamentation, fungal virulence, nitrogen limitation, basidiospores, cell morphology, immunosuppressants
MeSH terms: Mating Factor, Cryptococcus neoformans, Diploidy, Haploidy, Mutation, Peptides, Pheromones, Spores, Fungal, Transcription, Genetic, Gene Expression Regulation, Fungal, Tacrolimus, Cyclosporine, Genes, Reporter, Calcineurin, Protein Subunits, Calcineurin Inhibitors

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Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans

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