The ER Protein Translocation Channel Subunit Sbh1 Controls Virulence of Cryptococcus neoformans.
The ER Protein Translocation Channel Subunit Sbh1 Controls Virulence of Cryptococcus neoformans.
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作者：
真菌病原体新型隐球菌的特征在于细胞壁锚定的多糖荚膜，其对毒力至关重要。细胞壁和被膜的生物发生都依赖于分泌途径。蛋白质分泌开始于多肽通过高度保守的通道穿过内质网（ER）膜，该通道由三种蛋白质形成：Sec61，Sbh1和Sss1。Sbh1，最分歧的，包含多个磷酸化位点，这可能使其能够调节进入分泌途径中的物种和蛋白质特异性的方式。SBH 1的缺失导致酿酒酵母和C.新形式，虽然其他表型不同。值得注意的是，蛋白质组学分析表明，当隐球菌在模拟哺乳动物宿主环境的条件下（组织培养基，37°C，5%CO2）生长时，一组分泌和跨膜蛋白在野生型中上调，但在Δ sbh 1突变细胞中则没有。Sbh1依赖性蛋白质显示其ER靶向序列的特定特征，这可能导致它们不太有效地转运到分泌途径中。许多也在细胞壁生物发生中起作用，而一些是已知的毒力因子。与这些观察结果相一致，C。在小鼠感染模型中，neoformans Δ sbh 1突变体是无毒的。我们的结论是，在感染过程中遇到的条件下，Sbh1控制进入的毒力因子的分泌途径的C。neoformans，从而调节真菌致病性。
The fungal pathogen Cryptococcus neoformans is distinguished by a cell-wall-anchored polysaccharide capsule that is critical for virulence. Biogenesis of both cell wall and capsule relies on the secretory pathway. Protein secretion begins with polypeptide translocation across the endoplasmic reticulum (ER) membrane through a highly conserved channel formed by three proteins: Sec61, Sbh1, and Sss1. Sbh1, the most divergent, contains multiple phosphorylation sites, which may allow it to regulate entry into the secretory pathway in a species- and protein-specific manner. Absence of SBH1 causes a cell-wall defect in both Saccharomyces cerevisiae and C. neoformans, although other phenotypes differ. Notably, proteomic analysis showed that when cryptococci are grown in conditions that mimic aspects of the mammalian host environment (tissue culture medium, 37°C, 5% CO2), a set of secretory and transmembrane proteins is upregulated in wild-type, but not in Δsbh1 mutant cells. The Sbh1-dependent proteins show specific features of their ER targeting sequences that likely cause them to transit less efficiently into the secretory pathway. Many also act in cell-wall biogenesis, while several are known virulence factors. Consistent with these observations, the C. neoformans Δsbh1 mutant is avirulent in a mouse infection model. We conclude that, in the context of conditions encountered during infection, Sbh1 controls the entry of virulence factors into the secretory pathway of C. neoformans, and thereby regulates fungal pathogenicity.
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影响因子：
3.6
作者：
Gilbert NM;Donlin MJ;Gerik KJ;Specht CA;Djordjevic JT;Wilson CF;Sorrell TC;Lodge JK
通讯作者：
Lodge JK
影响因子：
6.4
作者：
Cadieux, Brigitte;Lian, Tianshun;Kronstad, James W.
通讯作者：
Kronstad, James W.
影响因子：
15.9
作者：
Besse, Whitney;Dong, Ke;Somlo, Stefan
通讯作者：
Somlo, Stefan
影响因子：
64.8
作者：
Besemer, J;Harant, H;Lindley, IJD
通讯作者：
Lindley, IJD
DOI：
10.1046/j.1432-1327.1999.00215.x
发表时间：
1999-03-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Gruss, OJ;Feick, P;Dobberstein, B
通讯作者：
Dobberstein, B