The Gβ-like protein CpcB is required for hyphal growth, conidiophore morphology and pathogenicity in Aspergillus fumigatus

The Gβ-like protein CpcB is required for hyphal growth, conidiophore morphology and pathogenicity in Aspergillus fumigatus
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G β 样蛋白 CpcB 是烟曲霉菌丝生长、分生孢子梗形态和致病性所必需的

DOI:
10.1016/j.fgb.2015.04.007
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发表时间:
2015-08-01
影响因子:
3
通讯作者:
Lu, Ling
Lu, Ling
中科院分区:
生物学3区
文献类型:
--
作者:
Cai, Zhen-dong;Chai, Yan-fei;Lu, Ling

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Cpc B(交叉途径对照B)编码酵母Cpc 2和哺乳动物RACK 1(活化蛋白激酶C受体)直系同源物,其是与烟曲霉中异源三聚体G蛋白的β亚基具有功能同源性的WD重复蛋白。以前的研究报道CpcB控制着A.烟曲霉和构巢曲霉。然而,很少有人知道CpcB的直系同源物的功能特性及其与G蛋白复合物的关系。在这项研究中,我们证实了胞质AfCpcB作为一个G β样蛋白的直系同源物,并在菌丝生长,分生孢子形态,细胞壁完整性和毒力在A.烟熏。此外,AfcpcB和AfgpaB(G α)的双缺失导致与具有异常多隔分生孢子梗的AfgpaB突变体相似的表型,但表现出具有白色和蓬松菌落的稀疏分生孢子。因此,加剧的分生孢子缺陷表明,AfcpcB具有其自身的特定功能相比,Got亚基的AfgpaB或G蛋白复合物。此外,使用A.构巢酵母和酵母(酿酒酵母、粟酒裂殖酵母、白色念珠菌)表明,所有测试的真菌AfcpcB直系同源物在A. Fumigatus天然启动子可以很好地恢复AfcpcB缺失突变体的菌丝生长缺陷,但只有A. nidulans cpcB直系同源物完全挽救了Δ AfcpcB分生孢子缺陷,这表明CpcB在真菌中充当G β样蛋白直系同源物,但可能具有酵母中不存在的分生孢子所需的独特且重要的未探索的功能。(C)2015 Elsevier Inc. All rights reserved.
CpcB (cross pathway control B) encodes a yeast Cpc2 and mammalian RACK1 (receptor for activated protein kinase C) ortholog, which is a WD repeat protein with functional homology to the beta subunit of heterotrimeric G proteins in Aspergillus fumigatus. Previous study has reported that CpcB governs growth and development in both A. fumigatus and Aspergillus nidulans. However, little is known about the functional identities of CpcB orthologs and their relationships with G protein complexes. In this study, we verified that cytoplasmic AfCpcB acts as a G beta-like protein ortholog and plays important roles in hyphal growth, conidiophore morphology, cell wall integrity, and virulence in A. fumigatus. Furthermore, double deletion of AfcpcB and AfgpaB (G alpha) causes a similar phenotype to AfgpaB mutant with abnormal multiple septa conidiophores but exhibits sparse conidiation with white and fluffy colonies. Thus, the exacerbated conidiation defect suggests that AfcpcB has its own specific function compared to the Got subunit of AfgpaB or the G-protein complex. In addition, complementation assays using AfcpcB orthologs of A. nidulans and yeasts (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans) suggest that all tested fungal AfcpcB orthologs under the A. fumigatus native promoter can largely restore hyphal growth defects in AfcpcB deletion mutant, but only the A. nidulans cpcB ortholog completely rescues the Delta AfcpcB conidiation defect, suggesting that CpcB acts as a G beta-like protein ortholog in the Aspergilli, but may have unique and important unexplored functions that required for conidiation, which is absent in yeast. (C) 2015 Elsevier Inc. All rights reserved.