DOI: 10.1101/gad.11.23.3206. <i>Cryptococcus neoformans</i> mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP

Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP

10.1101/gad.11.23.3206

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

This study explores signal transduction pathways that function during mating and infection in the opportunistic, human fungal pathogenCryptococcus neoformans. The gene encoding a G-protein α subunit homolog, GPA1, was disrupted by homologous recombination. The gpa1 mutant strain was viable but exhibited a defect in mating in response to nitrogen starvation. Additionally, the gpa1 mutant strain failed to induce two well-established virulence factors—melanin synthesis, in response to glucose starvation; and capsule production, in response to iron limitation. As a consequence, virulence of the gpa1 mutant strain was significantly attenuated in an animal model of cryptococcal meningitis. Reintroduction of the wild-type GPA1 gene complemented thegpa1 mutant phenotypes and restored mating, melanin and capsule production, and virulence. Similarly, exogenous cAMP also suppressed the gpa1 mutant phenotypes, restoring mating and production of melanin and capsule. These observations support a model in which GPA1 has a role in sensing diverse environmental signals required for mating and virulence by regulating cAMP metabolism in C. neoformans.

Bibliography

Alspaugh, J. A., Perfect, J. R., & Heitman, J. (1997). Cryptococcus neoformans mating and virulence are regulated by the G-protein Î± subunit GPA1 andâcAMP. Genes & Development, 11(23), 3206â3217.

Authors 3

J. Andrew Alspaugh (first)
John R. Perfect (additional)
Joseph Heitman (additional)

References 44 Referenced 355

10.1016/0968-0004(94)90147-3 / Trends Biosci. / Diversity in function and regulation of MAP kinase pathways. by Blumer (1994)
{'key': '2021111418494650000_11.23.3206.2', 'first-page': '4912', 'article-title': 'Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence.', 'volume': '14', 'author': 'Chang', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. by Chang (1994)
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10.1128/jb.150.3.1414-1421.1982 / J. Bacteriol. / Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice. by Kwon-Chung (1982)
10.1016/0955-0674(95)80028-X
Lorenz, M.C. and J. Heitman. 1997. Yeast pseudohyphal growth is regulated by GPA2, a G protein α homolog. EMBO J. (in press).. (10.1093/emboj/16.23.7008)
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{'key': '2021111418494650000_11.23.3206.23', 'first-page': '1962', 'article-title': 'The α-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene.', 'volume': '13', 'author': 'Moore', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The α-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene. by Moore (1993)
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10.1128/jb.176.3.656-664.1994 / J. Bacteriol. / Biochemical and molecular characterization of the diphenol oxidase of Cryptococcus neoformans: Identification as a laccase. by Williamson (1994)

Dates

Type	When
Created	17 years, 6 months ago (Feb. 20, 2008, 5:15 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 10:13 p.m.)
Indexed	5 days, 6 hours ago (Aug. 30, 2025, 12:50 p.m.)
Issued	27 years, 9 months ago (Dec. 1, 1997)
Published	27 years, 9 months ago (Dec. 1, 1997)
Published Online	27 years, 9 months ago (Dec. 1, 1997)
Published Print	27 years, 9 months ago (Dec. 1, 1997)

Funders 0

None

BibTeX

@article{Alspaugh_1997, title={Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP}, volume={11}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.11.23.3206}, DOI={10.1101/gad.11.23.3206}, number={23}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Alspaugh, J. Andrew and Perfect, John R. and Heitman, Joseph}, year={1997}, month=dec, pages={3206–3217} }

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