Lu Hui, Sun Yuan, Jiang Yuan-Ying, Whiteway Malcolm
Center for New Drug Research, Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
Eukaryot Cell. 2014 Apr;13(4):461-9. doi: 10.1128/EC.00320-13. Epub 2014 Jan 31.
Heterotrimeric G proteins are an important class of eukaryotic signaling molecules that have been identified as central elements in the pheromone response pathways of many fungi. In the fungal pathogen Candida albicans, the STE18 gene (ORF19.6551.1) encodes a potential γ subunit of a heterotrimeric G protein; this protein contains the C-terminal CAAX box characteristic of γ subunits and has sequence similarity to γ subunits implicated in the mating pathways of a variety of fungi. Disruption of this gene was shown to cause sterility of MTLa mating cells and to block pheromone-induced gene expression and shmoo formation; deletion of just the CAAX box residues is sufficient to inactivate Ste18 function in the mating process. Intriguingly, ectopic expression behind the strong ACT1 promoter of either the Gα or the Gβ subunit of the heterotrimeric G protein is able to suppress the mating defect caused by deletion of the Gγ subunit and restore both pheromone-induced gene expression and morphology changes.
异源三聚体G蛋白是一类重要的真核信号分子,已被确定为许多真菌信息素反应途径的核心元件。在真菌病原体白色念珠菌中,STE18基因(ORF19.6551.1)编码一种潜在的异源三聚体G蛋白γ亚基;该蛋白含有γ亚基特有的C末端CAAX框,并且与多种真菌交配途径中涉及的γ亚基具有序列相似性。已表明破坏该基因会导致MTLa交配细胞不育,并阻断信息素诱导的基因表达和shmoo形成;仅缺失CAAX框残基就足以使Ste18在交配过程中的功能失活。有趣的是,异源三聚体G蛋白的Gα或Gβ亚基在强ACT1启动子后异位表达能够抑制因Gγ亚基缺失而导致的交配缺陷,并恢复信息素诱导的基因表达和形态变化。