Allelic exchange of pheromones and their receptors reprograms sexual identity in Cryptococcus neoformans.
Allelic exchange of pheromones and their receptors reprograms sexual identity in Cryptococcus neoformans.
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DOI：
10.1371/journal.pgen.1000860
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发表时间：
2010-02-26
期刊：
影响因子：
4.5
通讯作者：
Hull CM
中科院分区：
文献类型：
--
作者：
Stanton BC;Giles SS;Staudt MW;Kruzel EK;Hull CM
细胞类型特化是所有细胞必须进行的基本过程，以确保响应环境刺激的适当行为。在真菌中，细胞身份对于定义称为交配型的“性别”至关重要，并且由交配型（MAT）基因座的组成部分控制。MAT编码的基因通过两种不同的模式来定义性别：1）通过控制两性共有成分的转录，或2）通过表达在交配类型之间不同的特殊编码因子（信息素及其受体）。人类真菌病原体新型隐球菌有两种交配类型（a和α），由一个极其不寻常的MAT基因座指定。这个基因座的复杂结构使得我们无法预测哪种模式控制交配类型。探讨C.在确定了新形虫的性别后，我们建立了一个品系，其中来自一个交配型的信息素和信息素受体（a）取代了另一个交配型的信息素和信息素受体（α）。我们发现这些“αa”细胞有效地采用了一种新的交配类型（a细胞的交配类型）;它们感知α因子并对其做出反应，它们引起α细胞的交配反应，并与α细胞融合。此外，αa细胞失去了对信息素的α细胞类型特异性反应，并且不形成芽管，而是保持像α细胞一样的球形。最后，我们发现二倍体/双核体特异性转录因子Sxi 2a的外源表达可以促进α和αa菌株之间的杂交中的完全性发育。这些数据揭示了C.新形虫的基因完全由三种MAT编码的蛋白质控制：信息素、信息素受体和同源结构域蛋白。我们的研究结果建立了这种不寻常的人类真菌病原体维持不同细胞类型和随后发育行为的机制。所有进行有性生殖的生物都有特定的机制来建立不同的性别。在真菌中，性别身份通常由位于染色体特定区域内的成分决定，称为交配型（MAT）基因座。MAT编码的基因通过两种不同的模式来定义性别：1）通过控制两性共有成分的转录，或2）通过表达在交配类型之间不同的特殊编码因子（信息素及其受体）。新型隐球菌的两种交配类型（a和α）由一个极其不寻常的MAT基因座所指定。这个基因座的独特结构使我们无法预测哪种模式控制交配类型。探讨C.在确定了新形虫的性别后，我们创建了一个α菌株，其中信息素和信息素受体被来自a菌株的类似基因所取代。我们发现，由此产生的应变（αa）现在表现得好像它是一个a。它感知α细胞并作出反应，与α细胞交配，不再表现出其他α特异性行为。我们的数据表明，两个且只有两个基因的替换完全改变了α细胞的性别身份，建立了信息素及其受体作为C.新人类
Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining “sexes” known as mating types and is controlled by components of mating type (MAT) loci. MAT–encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and α) that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a) replaced the pheromone and pheromone receptor of the other (α). We discovered that these “αa” cells effectively adopt a new mating type (that of a cells); they sense and respond to α factor, they elicit a mating response from α cells, and they fuse with α cells. In addition, αa cells lose the α cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between α and αa strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT–encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen. All organisms that undergo sexual reproduction carry out specific mechanisms to establish different sexes. In fungi, sexual identity is typically determined by components housed within specialized regions of chromosomes known as mating-type (MAT) loci. MAT–encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The two mating types of Cryptococcus neoformans (a and α) are specified by an extremely unusual MAT locus. The unique architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created an α strain where the pheromones and pheromone receptor were replaced with the analogous genes from an a strain. We discovered that the resulting strain (αa) now behaves as if it is an a. It senses and responds to α cells, mates with α cells, and no longer exhibits other α-specific behaviors. Our data show that replacement of two and only two genes completely alters the sexual identity of α cells, establishing pheromones and their receptors as the determinants of sexual identity in C. neoformans.
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影响因子：
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