Frawley Dean, Stroe Maria C, Oakley Berl R, Heinekamp Thorsten, Straßburger Maria, Fleming Alastair B, Brakhage Axel A, Bayram Özgür
Department of Biology, Fungal Genetics and Secondary Metabolism Laboratory, Maynooth University, Maynooth, Ireland.
Department of Molecular and Applied Microbiology, Hans Knöll Institute (HKI), Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.
Front Microbiol. 2020 May 7;11:811. doi: 10.3389/fmicb.2020.00811. eCollection 2020.
In order for eukaryotes to efficiently detect and respond to environmental stimuli, a myriad of protein signaling pathways are utilized. An example of highly conserved signaling pathways in eukaryotes are the mitogen-activated protein kinase (MAPK) pathways. In fungi, MAPK pathways have been shown to regulate a diverse array of biological processes, such as asexual and sexual development, stress responses and the production of secondary metabolites (SMs). In the model fungus , a MAPK pathway known as the pheromone module is utilized to regulate both development and SM production. This signaling cascade consists of the three kinases SteC, MkkB, and MpkB, as well as the SteD adaptor protein and the HamE scaffold. In this study, homologs of each of these proteins have been identified in the opportunistic human pathogen By performing epitope tagging and mass spectrometry experiments, we have shown that these proteins form a pentameric complex, similar to what is observed in This complex has been shown to assemble in the cytoplasm and MpkB enters the nucleus, where it would presumably interact with various transcription factors. Pheromone module mutant strains exhibit drastic reductions in asexual sporulation, vegetative growth rate and production of SMs, such as gliotoxin. Mutants also display increased sensitivity to cell wall and oxidative stress agents. Overall, these data provide evidence of the existence of a conserved MAP kinase signaling pathway in species and suggest that this pathway is critical for the regulation of fungal development and secondary metabolism.
为了使真核生物能够有效地检测并响应环境刺激，需利用众多蛋白质信号通路。真核生物中高度保守的信号通路的一个例子是丝裂原活化蛋白激酶（MAPK）通路。在真菌中，MAPK通路已被证明可调节多种生物过程，如无性和有性发育、应激反应以及次级代谢产物（SMs）的产生。在模式真菌中，一种称为信息素模块的MAPK通路被用于调节发育和SMs的产生。这个信号级联由三种激酶SteC、MkkB和MpkB，以及SteD衔接蛋白和HamE支架组成。在本研究中，已在机会性人类病原体中鉴定出这些蛋白质各自的同源物。通过进行表位标记和质谱实验，我们已表明这些蛋白质形成了一个五聚体复合物，类似于在中观察到的情况。该复合物已被证明在细胞质中组装，并且MpkB进入细胞核，在那里它可能会与各种转录因子相互作用。信息素模块突变菌株在无性孢子形成、营养生长速率和SMs（如gliotoxin）的产生方面表现出大幅降低。突变体对细胞壁和氧化应激剂也表现出更高的敏感性。总体而言，这些数据提供了在物种中存在保守的MAP激酶信号通路的证据，并表明该通路对于真菌发育和次级代谢的调节至关重要。
