Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans
Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans
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DOI：
10.1093/emboj/20.5.1020
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发表时间：
2001-03-01
期刊：
影响因子：
11.4
通讯作者：
Heitman, J
中科院分区：
文献类型：
--
作者：
Cruz, MC;Fox, DS;Heitman, J
新型隐球菌是一种真菌病原体，可导致免疫功能低下患者的脑膜炎。其生长对免疫抑制剂FK 506和环孢菌素敏感，其抑制Ca 2 +-钙调蛋白激活的蛋白磷酸酶钙调神经磷酸酶。钙调神经磷酸酶是在37 ℃生长和新型隐球菌毒力所必需的。我们发现钙调神经磷酸酶也是交配所必需的。FK 506通过FKBP 12依赖性抑制钙调磷酸酶阻断新生隐球菌的交配，缺乏钙调磷酸酶的突变体是双侧不育的。钙调神经磷酸酶对于初始融合事件不是必需的，但是对于由细胞融合产生的异核体的菌丝伸长和存活是必需的。它也是二倍体菌株中的菌丝伸长和响应于氮限制的MAT α细胞的无性单倍体结实期间所必需的。由于交配和单倍体结实产生感染性担孢子，我们的研究表明钙调神经磷酸酶和新生隐球菌的毒力之间的第二个联系。钙调神经磷酸酶通过不同的途径调节诱导和37 ℃生长。连同研究表明，钙调神经磷酸酶介导的神经突起的延伸和中性粒细胞的迁移在哺乳动物中，我们的研究结果表明，钙调神经磷酸酶在细胞形态的控制中起着保守的作用。
Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised patients. Its growth is sensitive to the immunosuppressants FK506 and cyclosporin, which inhibit the Ca2+-calmodulin-activated protein phosphatase calcineurin. Calcineurin is required for growth at 37 degreesC and virulence of C.neoformans. We found that calcineurin is also required for mating. FK506 blocks mating of C.neoformans via FKBP12-dependent inhibition of calcineurin, and mutants lacking calcineurin are bilaterally sterile. Calcineurin is not essential for the initial fusion event, but is required for hyphal elongation and survival of the heterokaryon produced by cell fusion, It is also required for hyphal elongation in diploid strains and during asexual haploid fruiting of MAT alpha cells in response to nitrogen limitation. Because mating and haploid fruiting produce infectious basidiospores, our studies suggest a second link between calcineurin and virulence of C.neoformans. Calcineurin regulates filamentation and 37 degreesC growth via distinct pathways. Together with studies revealing that calcineurin mediates neurite extension and neutrophil migration in mammals, our findings indicate that calcineurin plays a conserved role in the control of cell morphology.