Comparative proteomic analysis of Gib2 validating its adaptor function in Cryptococcus neoformans.
Comparative proteomic analysis of Gib2 validating its adaptor function in Cryptococcus neoformans.
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DOI：
10.1371/journal.pone.0180243
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Bruni GO;Battle B;Kelly B;Zhang Z;Wang P
新型隐球菌引起免疫功能低下个体的真菌性脑膜脑炎。虽然确切的发病机制仍然不清楚，但已知由关键元件如G蛋白α亚基Gpa 1、小GT3 Ras 1和非典型Gβ样/RACK 1蛋白Gib 2介导的信号转导途径在C.新形虫毒力Gib 2对于正常生长、分化和致病性是重要的，并且它还与Gpa 1一起正向调节cAMP水平。有趣的是，Gib 2通过与多种细胞蛋白相互作用而显示支架蛋白性质。为了探索Gib 2的全局调控功能，我们进行了二维差异凝胶电泳（DIGE）分析，发现GIB 2破坏导致304个蛋白点（43.4%）的表达增加和396个蛋白点（56.6%）的表达减少。对96种表达变化被认为显著（≥ +/- 1.5倍）的蛋白质的分析显示，75种蛋白质属于至少12个功能蛋白质组。其中，8组具有p ≤ 0.05的统计严格性，并且包括热休克蛋白70/71同源物和核糖体蛋白的4组存活于Bonferroni校正。这一发现与人类Gβ样/RACK 1和芽殖酵母酿酒酵母Asc 1的早期作用一致。这表明Gib 2也可能是影响C.新人类由于真核Hsp 70/71蛋白参与促进新生蛋白质折叠、加工和保护细胞免受胁迫，我们还提出Gib 2调节的胁迫反应与真菌毒力有关。总的来说，我们的研究支持Gβ样/RACK/Gib 2蛋白在核糖体生物合成和蛋白质翻译的基本细胞过程中的保守作用。我们的研究还强调了Gib 2在C.新人类
Cryptococcus neoformans causes often-fatal fungal meningoencephalitis in immunocompromised individuals. While the exact disease mechanisms remain elusive, signal transduction pathways mediated by key elements such as G-protein α subunit Gpa1, small GTPase Ras1, and atypical Gβ-like/RACK1 protein Gib2 are known to play important roles in C. neoformans virulence. Gib2 is important for normal growth, differentiation, and pathogenicity, and it also positively regulates cAMP levels in conjunction with Gpa1. Interestingly, Gib2 displays a scaffold protein property by interacting with a wide variety of cellular proteins. To explore Gib2 global regulatory functions, we performed two-dimensional differential gel electrophoresis (DIGE) analysis and found that GIB2 disruption results in an increased expression of 304 protein spots (43.4%) and a decreased expression of 396 protein spots (56.6%). Analysis of 96 proteins whose expression changes were deemed significant (≥ +/- 1.5- fold) revealed that 75 proteins belong to at least 12 functional protein groups. Among them, eight groups have the statistical stringency of p ≤ 0.05, and four groups, including Hsp70/71 heat shock protein homologs and ribosomal proteins, survived the Bonferroni correction. This finding is consistent with earlier established roles for the human Gβ-like/RACK1 and the budding yeast Saccharomyces cerevisiae Asc1. It suggests that Gib2 could also be part of the complex affecting ribosomal biogenesis and protein translation in C. neoformans. Since eukaryotic Hsp70/71 proteins are involved in the facilitation of nascent protein folding, processing, and protection of cells against stress, we also propose that Gib2-regulated stress responses are linked to fungal virulence. Collectively, our study supports a conserved role of Gβ-like/RACK/Gib2 proteins in the essential cellular process of ribosomal biogenesis and protein translation. Our study also highlights a multifaceted regulatory role of Gib2 in the growth and pathogenicity of C. neoformans.
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