Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans
Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans
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DOI：
10.1128/ec.1.3.366-377.2002
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发表时间：
2002-06-01
期刊：
影响因子：
--
通讯作者：
Heitman, J
中科院分区：
文献类型：
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作者：
Shen, WC;Davidson, RC;Heitman, J
新型隐球菌是一种致病性真菌，具有明确的性周期，涉及单倍体MAT α和MAT α细胞。有趣的是，MATalpha菌株更常见，比同类MATa菌株更具毒性，并且响应于氮限制或MATa细胞而经历单倍体结实。三个基因编码的MF α信息素被确定在MATalpha交配型基因座，并显示出转录诱导的限制营养和共培养与MATa细胞。MFalpha1、MFalpha2和MFalpha3基因单独和组合突变。缺乏Woe信息素的MATalpha菌株未能诱导MATa细胞的形态学变化。无信息素的MAT α突变体融合和交配受损，但不不育，交配水平接近野生型的1%。无信息素的MAT α突变体在单倍体结实中也有部分缺陷，并且MF α信息素的过表达增强了单倍体结实。MFa信息素的过表达也增强了MATalpha细胞的单倍体结实，并刺激MATa细胞中接合管的形成。发现保守的G蛋白激活的有丝分裂原激活的蛋白激酶信号通路是诱导和响应交配信息素所必需的。MF α信息素对C.但确实有助于整体毒力复合物。这些研究定义了旁分泌和自分泌信息素反应途径，信号交配和分化的这种致病真菌。
Cryptococcus neoformans is a pathogenic fungus with a defined sexual cycle involving haploid MATalpha and MATa cells. Interestingly, MATalpha strains are more common, are more virulent than congenic MATa strains, and undergo haploid fruiting in response to nitrogen limitation or MATa cells. Three genes encoding the MFalpha pheromone were identified in the MATalpha mating-type locus and shown to be transcriptionally induced by limiting nutrients and coculture with MATa cells. The MFalpha1, MFalpha2, and MFalpha3 genes were mutated, individually and in combination. MATalpha strains lacking Woe pheromone failed to induce morphological changes in MATa cells. Pheromoneless MATalpha mutants were fusion and mating impaired but not sterile and mated at similar to1% the wild-type level. The pheromoneless MATalpha mutants were also partially defective in haploid fruiting, and overexpression of MFalpha pheromone enhanced haploid fruiting. Overexpression of MFa pheromone also enhanced haploid fruiting of MATalpha cells and stimulated conjugation tube formation in MATa cells. A conserved G-protein activated mitogen-activated protein kinase signaling pathway was found to be required for both induction and response to mating pheromones. The MFalpha pheromone was not essential for virulence of C. neoformans but does contribute to the overall virulence composite. These studies define paracrine and autocrine pheromone response pathways that signal mating and differentiation of this pathogenic fungus.