Department of Biological Sciences, State University of New York at the University at Buffalo, New York 14260-1300.
Department of Chemical and Biological Engineering, State University of New York at the University at Buffalo, New York 14260-1300.
Genetics. 2019 Jul;212(3):667-690. doi: 10.1534/genetics.119.302004. Epub 2019 May 3.
Signaling pathways can regulate biological responses by the transcriptional regulation of target genes. In yeast, multiple signaling pathways control filamentous growth, a morphogenetic response that occurs in many species including fungal pathogens. Here, we examine the role of signaling pathways that control filamentous growth in regulating adhesion-dependent surface responses, including mat formation and colony patterning. Expression profiling and mutant phenotype analysis showed that the major pathways that regulate filamentous growth [filamentous growth MAPK (fMAPK), RAS, retrograde (RTG), RIM101, RPD3, ELP, SNF1, and PHO85] also regulated mat formation and colony patterning. The chromatin remodeling complex, SAGA, also regulated these responses. We also show that the RAS and RTG pathways coregulated a common set of target genes, and that SAGA regulated target genes known to be controlled by the fMAPK, RAS, and RTG pathways. Analysis of surface growth-specific targets identified genes that respond to low oxygen, high temperature, and desiccation stresses. We also explore the question of why cells make adhesive contacts in colonies. Cell adhesion contacts mediated by the coregulated target and adhesion molecule, Flo11p, deterred entry into colonies by macroscopic predators and impacted colony temperature regulation. The identification of new regulators (, SAGA), and targets of surface growth in yeast may provide insights into fungal pathogenesis in settings where surface growth and adhesion contributes to virulence.
信号通路可以通过靶基因的转录调控来调节生物反应。在酵母中,多种信号通路控制丝状生长,这是一种形态发生反应,发生在包括真菌病原体在内的许多物种中。在这里,我们研究了控制丝状生长的信号通路在调节粘附依赖性表面反应(包括基质形成和菌落图案化)中的作用。表达谱分析和突变体表型分析表明,调节丝状生长的主要途径[丝状生长 MAPK(fMAPK)、RAS、逆行(RTG)、RIM101、RPD3、ELP、SNF1 和 PHO85]也调节基质形成和菌落图案化。染色质重塑复合物 SAGA 也调节了这些反应。我们还表明,RAS 和 RTG 途径共同调节了一组共同的靶基因,并且 SAGA 调节了已知受 fMAPK、RAS 和 RTG 途径控制的靶基因。对表面生长特异性靶基因的分析鉴定了响应低氧、高温和干燥胁迫的基因。我们还探讨了细胞在菌落中形成粘附接触的原因。由共同调节的靶基因和粘附分子 Flo11p 介导的细胞粘附接触阻止了宏观捕食者进入菌落,并影响了菌落的温度调节。在酵母中发现新的表面生长调节剂(如 SAGA)和靶标,可能为表面生长和粘附有助于毒力的真菌发病机制提供新的见解。