The Kinetochore Protein Spc105, a Novel Interaction Partner of LaeA, Regulates Development and Secondary Metabolism in Aspergillus flavus
The Kinetochore Protein Spc105, a Novel Interaction Partner of LaeA, Regulates Development and Secondary Metabolism in Aspergillus flavus
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动粒蛋白 Spc105 是 LaeA 的新型相互作用伙伴，调节黄曲霉的发育和次级代谢
DOI：
10.3389/fmicb.2019.01881
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发表时间：
2018-12
影响因子：
5.2
通讯作者：
He Zhu Mei
中科院分区：
文献类型：
--
作者：
Zhi Qing Qing;He Lei;Li Jie Ping;Li Jing;Wang Zhen Long;He Guang Yao;He Zhu Mei
核蛋白LaeA被认为是曲霉次生代谢的全局调节剂。LaeA与VeA和VelB连接形成异源三聚体，协调真菌的发育和次生代谢。在这里，我们描述了LaeA的一个新的相互作用伙伴，即从产生黄曲霉的真菌黄曲霉中提取的着丝点蛋白Spc105。我们发现，除了参与核分裂，sp105也是黄曲霉正常分生孢子发育和菌核形成所必需的。此外，Spc105正调控黄曲霉毒素和曲酸等次生代谢产物的产生，负调控环吡唑酸的产生。对Δspc105菌株的转录组分析显示，23个骨干基因差异表达，对应于56个次级代谢产物基因簇中的19个，表明Spc105在次级代谢中具有广泛的调控作用。值得注意的是，我们的转录组数据中laeA的表达减少导致了Spc105和laeA之间的相关性，双突变分析表明Spc105和laeA之间在功能上相互依赖。此外，酵母双杂交（Y2H）和GST下拉实验表明，Spc105直接与LaeA的s -腺苷蛋氨酸（SAM）结合域相互作用，并且Spc105中的亮氨酸拉链基序是这种相互作用所必需的。本研究发现的Spc105-LaeA相互作用表明黄曲霉中不同调节因子的合作相互作用，为真菌次级代谢调节网络提供了新的见解。黄曲霉毒素污染引起的农业和食品安全问题引起了人们对黄曲霉毒素生物合成调控的关注，黄曲霉毒素已成为探索真菌次生代谢调控的一种模式。在曲霉中，核蛋白LaeA被认为是次级代谢的全局调节剂，与VeA和VelB组成调控单元。LaeA被认为是通过改变染色质结构调控次生代谢的表观遗传机制，但其具体机制尚不清楚。我们在黄曲霉中发现了LaeA的一个新的相互作用伙伴，即着丝点蛋白Spc105。我们首次报道了该着丝点蛋白在真菌发育和黄曲霉毒素合成中的调控作用，并证明了其与LaeA的相互依赖关系。发现这样一个保守的细胞分裂相关基因调控黄曲霉的次生代谢，将为真菌次生代谢调控提供新的见解，并提高我们对LaeA相关网络的认识。
Nuclear protein LaeA is known as the global regulator of secondary metabolism in Aspergillus. LaeA connects with VeA and VelB to form a heterotrimeric complex, which coordinates fungal development and secondary metabolism. Here, we describe a new interaction partner of LaeA, the kinetochore protein Spc105, from the aflatoxin-producing fungus Aspergillus flavus. We showed that in addition to involvement in nuclear division, Spc105 is required for normal conidiophore development and sclerotia production of A. flavus. Moreover, Spc105 positively regulates the production of secondary metabolites such as aflatoxin and kojic acid, and negatively regulates the production of cyclopiazonic acid. Transcriptome analysis of the Δspc105 strain revealed that 23 backbone genes were differentially expressed, corresponding to 19 of the predicted 56 secondary metabolite gene clusters, suggesting a broad regulatory role of Spc105 in secondary metabolism. Notably, the reduced expression of laeA in our transcriptome data led to the discovery of the correlation between Spc105 and LaeA, and double mutant analysis indicated a functional interdependence between Spc105 and LaeA. Further, yeast two-hybrid (Y2H) and GST pull-down assays revealed that Spc105 interacts directly with the S-adenosylmethionine (SAM)-binding domain of LaeA, and that the leucine zipper motif in Spc105 is required for this interaction. The Spc105-LaeA interaction identified in our study indicates a cooperative interplay of distinct regulators in A. flavus, providing new insights into fungal secondary metabolism regulation networks. Author summary The worldwide concern on agriculture and food safety due to aflatoxin contamination has prompted increasing interest in understanding aflatoxin biosynthesis regulation that has become a model for exploring secondary metabolism regulation in fungi. In Aspergillus, the nuclear protein LaeA is considered as a global regulator of secondary metabolism that forms a regulatory unit with VeA and VelB. LaeA is proposed to control secondary metabolism epigenetically through altering the chromatin structure for gene expression, however, the exact mechanism is still enigmatic. Here we identified a new interaction partner of LaeA, a kinetochore protein Spc105, in aflatoxigenic Aspergillus flavus. We presented a regulatory role of this kinetochore protein in fungal development and aflatoxin biosynthesis for the first time, and demonstrated its interdependent relationship with LaeA. The finding that such a conserved cell division related gene regulates A. flavus secondary metabolism will offer new insights into the fungal secondary metabolism regulation and improve our understanding of LaeA involved networks.
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影响因子：
11.8
作者：
Meadows, John C.;Shepperd, Lindsey A.;Vanoosthuyse, Vincent;Lancaster, Theresa C.;Sochaj, Alicja M.;Buttrick, Graham J.;Hardwick, Kevin G.;Millar, Jonathan B. A.
通讯作者：
Millar, Jonathan B. A.
DOI：
10.1038/nrm3494
发表时间：
2013-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Palmer, Jonathan M.;Keller, Nancy P.
通讯作者：
Keller, Nancy P.
影响因子：
46.9
作者：
Trapnell C;Williams BA;Pertea G;Mortazavi A;Kwan G;van Baren MJ;Salzberg SL;Wold BJ;Pachter L
通讯作者：
Pachter L
影响因子：
5.2
作者：
Calvo AM;Cary JW
通讯作者：
Cary JW