Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260-1300, USA.
Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School, Houston, TX 77030, USA.
Genetics. 2024 Oct 7;228(2). doi: 10.1093/genetics/iyae122.
Eukaryotic organisms are composed of different cell types with defined shapes and functions. Specific cell types are produced by the process of cell differentiation, which is regulated by signal transduction pathways. Signaling pathways regulate cell differentiation by sensing cues and controlling the expression of target genes whose products generate cell types with specific attributes. In studying how cells differentiate, fungi have proved valuable models because of their ease of genetic manipulation and striking cell morphologies. Many fungal species undergo filamentous growth-a specialized growth pattern where cells produce elongated tube-like projections. Filamentous growth promotes expansion into new environments, including invasion into plant and animal hosts by fungal pathogens. The same signaling pathways that regulate filamentous growth in fungi also control cell differentiation throughout eukaryotes and include highly conserved mitogen-activated protein kinase (MAPK) pathways, which is the focus of this review. In many fungal species, mucin-type sensors regulate MAPK pathways to control filamentous growth in response to diverse stimuli. Once activated, MAPK pathways reorganize cell polarity, induce changes in cell adhesion, and promote the secretion of degradative enzymes that mediate access to new environments. However, MAPK pathway regulation is complicated because related pathways can share components with each other yet induce unique responses (i.e. signal specificity). In addition, MAPK pathways function in highly integrated networks with other regulatory pathways (i.e. signal integration). Here, we discuss signal specificity and integration in several yeast models (mainly Saccharomyces cerevisiae and Candida albicans) by focusing on the filamentation MAPK pathway. Because of the strong evolutionary ties between species, a deeper understanding of the regulation of filamentous growth in established models and increasingly diverse fungal species can reveal fundamentally new mechanisms underlying eukaryotic cell differentiation.
真核生物由具有特定形状和功能的不同细胞类型组成。特定的细胞类型是通过细胞分化过程产生的，而细胞分化过程受信号转导途径的调节。信号通路通过感知线索和控制靶基因的表达来调节细胞分化，其产物产生具有特定属性的细胞类型。在研究细胞分化时，真菌因其易于遗传操作和惊人的细胞形态而被证明是有价值的模型。许多真菌物种经历丝状生长——一种特殊的生长模式，其中细胞产生伸长的管状突起。丝状生长促进向新环境扩展，包括真菌病原体入侵植物和动物宿主。调节真菌丝状生长的相同信号通路也控制真核生物中的细胞分化，包括高度保守的丝裂原激活蛋白激酶 (MAPK) 通路，这是本综述的重点。在许多真菌物种中，粘蛋白型传感器调节 MAPK 通路以响应各种刺激控制丝状生长。一旦被激活，MAPK 通路会重新组织细胞极性，诱导细胞黏附的变化，并促进降解酶的分泌，从而介导进入新环境。然而，MAPK 通路的调节很复杂，因为相关通路可以相互共享组件，但诱导独特的反应（即信号特异性）。此外，MAPK 通路与其他调节途径（即信号整合）在高度集成的网络中发挥作用。在这里，我们通过关注丝状生长 MAPK 通路，在几个酵母模型（主要是酿酒酵母和白色念珠菌）中讨论信号特异性和整合。由于物种之间存在强大的进化联系，因此深入了解既定模型和日益多样化的真菌物种中丝状生长的调节可以揭示真核细胞分化的基本新机制。
