{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:44:31Z","timestamp":1790037871972,"version":"4.0.1"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"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":[[2006,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The ability of\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    to grow at the mammalian body temperature (37\u00b0C to 39\u00b0C) is a well-established virulence factor. Growth of\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    at this physiological temperature requires calcineurin, a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/calmodulin-dependent protein phosphatase. When cytosolic calcium concentrations are low (\u223c50 to 100 nM), calcineurin is inactive and becomes active only when cytosolic calcium concentrations rise (\u223c1 to 10 \u03bcM) through the activation of calcium channels. In this study we analyzed the function of Cch1 in\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    and found that Cch1 is a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -permeable channel that mediates calcium entry in\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    . Analysis of the Cch1 protein sequence revealed differences in the voltage sensor (S4 regions), suggesting that Cch1 may have diminished voltage sensitivity or possibly an alternative gating mechanism. The inability of the\n                    <jats:italic>cch1<\/jats:italic>\n                    mutant to grow under conditions of limited extracellular calcium concentrations ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>extracellular<\/jats:sub>\n                    , \u223c100 nM) suggested that Cch1 was required for calcium uptake in low-calcium environments. These results are consistent with the role of ScCch1 in mediating high-affinity calcium uptake in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    . Although the growth defect of the\n                    <jats:italic>cch1<\/jats:italic>\n                    mutant under conditions of limited [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>extracellular<\/jats:sub>\n                    (\u223c100 nM) became more severe with increasing temperature (25\u00b0C to 38.5\u00b0), this temperature sensitivity was not observed when the\n                    <jats:italic>cch1<\/jats:italic>\n                    mutant was grown on rich medium ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>extracellular<\/jats:sub>\n                    , \u223c0.140 mM). Accordingly, the\n                    <jats:italic>cch1<\/jats:italic>\n                    mutant strain displayed only attenuated virulence when tested in the mouse inhalation model of cryptococcosis, further suggesting that\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    may have a limited requirement for Cch1 and that this requirement appears to include ion stress tolerance.\n                  <\/jats:p>","DOI":"10.1128\/ec.00158-06","type":"journal-article","created":{"date-parts":[[2006,10,9]],"date-time":"2006-10-09T19:00:38Z","timestamp":1160420438000},"page":"1788-1796","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":73,"title":["Cch1 Mediates Calcium Entry in\n                    <i>Cryptococcus neoformans<\/i>\n                    and Is Essential in Low-Calcium Environments"],"prefix":"10.1128","volume":"5","author":[{"given":"Min","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology and Toxicology, University of California, Davis, Genome and Biomedical Sciences Facility, Davis, California 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Toxicology, University of California, Davis, Genome and Biomedical Sciences Facility, Davis, California 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie","family":"Gelli","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Toxicology, University of California, Davis, Genome and Biomedical Sciences Facility, Davis, California 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2137(01)80011-X"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(03)00066-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.38.23357"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35036035"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.3.422-430.2003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.10.2343"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-02-0113"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.521"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.443-448.2000"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02236.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.35.102401.091302"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2607"},{"key":"e_1_3_2_14_2","unstructured":"Duke IGSP Center for Applied Genomics and Technology. 2006. 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