{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:42:46Z","timestamp":1791873766916,"version":"4.3.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The titan cell is a recently described morphological form of the pathogenic fungus\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n                    . 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\n                    <jats:bold>a<\/jats:bold>\n                    pheromone receptor (in mating type\n                    <jats:bold>a<\/jats:bold>\n                    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\n                    <jats:sub>1<\/jats:sub>\n                    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.\n                  <\/jats:p>","DOI":"10.1128\/ec.05179-11","type":"journal-article","created":{"date-parts":[[2011,8,5]],"date-time":"2011-08-05T22:04:52Z","timestamp":1312581892000},"page":"1306-1316","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":119,"title":["Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli"],"prefix":"10.1128","volume":"10","author":[{"given":"Laura H.","family":"Okagaki","sequence":"first","affiliation":[{"name":"Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Wang","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Ballou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa R.","family":"O'Meara","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Sun","family":"Bahn","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Center for Fungal Pathogenesis, Yonsei University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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