{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:25:49Z","timestamp":1791959149627,"version":"4.3.4"},"reference-count":44,"publisher":"Cold Spring Harbor Laboratory","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1997,12,1]]},"abstract":"<jats:p>This study explores signal transduction pathways that function during mating and infection in the opportunistic, human fungal pathogen<jats:italic>Cryptococcus neoformans.<\/jats:italic> The gene encoding a G-protein \u03b1 subunit homolog, <jats:italic>GPA1,<\/jats:italic> was disrupted by homologous recombination. The <jats:italic>gpa1<\/jats:italic> mutant strain was viable but exhibited a defect in mating in response to nitrogen starvation. Additionally, the <jats:italic>gpa1<\/jats:italic> mutant strain failed to induce two well-established virulence factors\u2014melanin synthesis, in response to glucose starvation; and capsule production, in response to iron limitation. As a consequence, virulence of the <jats:italic>gpa1<\/jats:italic> mutant strain was significantly attenuated in an animal model of cryptococcal meningitis. Reintroduction of the wild-type <jats:italic>GPA1<\/jats:italic> gene complemented the<jats:italic>gpa1<\/jats:italic> mutant phenotypes and restored mating, melanin and capsule production, and virulence. Similarly, exogenous cAMP also suppressed the <jats:italic>gpa1<\/jats:italic> 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 <jats:italic>C. neoformans.<\/jats:italic><\/jats:p>","DOI":"10.1101\/gad.11.23.3206","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T22:15:26Z","timestamp":1203545726000},"page":"3206-3217","source":"Crossref","is-referenced-by-count":367,"title":["<i>Cryptococcus neoformans<\/i> mating and virulence are regulated by the G-protein \u03b1 subunit GPA1 and\u2009cAMP"],"prefix":"10.1101","volume":"11","author":[{"given":"J. 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