Components, dynamics and effectors of the MAK2 MAP kinase cascade

MAK2 MAP 激酶级联的组成、动力学和效应子

• 批准号: 258036129
• 负责人: Privatdozent Dr. Stephan Seiler
• 金额: --
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/258036129?language=en
• 关键词: Components; dynamics; effectors; MAK2; MAP

Background: Communication among microbes is a fundamental biological problem. Filamentous fungi that secrete a vast array of metabolites and putative signaling molecules are excellent model systems to address this problem. The connection between chemical gradient sensing and regulation of cell polarity is only poorly understood in any eukaryotic system. In Neurospora crassa an unknown chemical ligand mediates chemotropic interactions resulting in cell fusion of genetically identical cells. This process of self-signaling is based on the oscillatory recruitment of the MAK2 MAP kinase cascade to the opposing tips of communicating cells. The rapid alternation of these two different physiological states of homing cells likely reflects signal delivery and response. Objectives: Our mechanistic understanding of oscillatory MAK2 signaling is hampered by the fact that most components of the signaling machinery, including a postulated secreted signal and its cognate receptor, regulators of the MAP kinase cascade as well as MAK2 targets, are unknown. The long-term goal of this research project is the mechanistic understanding of pulsatile MAK2 signaling. The specific objectives for the proposal are (i) defining components, dynamics and regulation of the MAK2 cascade, and (ii) characterizing MAK2 pathway effectors that guide the chemotrophic growth response. Significance: Hyphal fusion is comparable to cell fusion between genetically identical cells of higher eukaryotes, which results in the formation of multinuclear syncytia. Important examples for human biology are myoblast fusion during muscle differentiation, trophoblast fusion during placental development and osteoclast fusion during bone formation. Thus, fungal self-signaling provides a useful model for understanding molecular mechanisms of cell communication in more complex organisms. Moreover, intercellular communication and somatic cell fusion is important for establishment and function of the fungal colony by sharing nutrients and organelles of individual cells. Hyphal anastomosis is thus also critical for host colonization and virulence of pathogenic fungi. Understanding this process will have significant implications on our ability to intervene in this process by either inhibiting it in cases of detrimental fungi or enhancing it when beneficial growth is desired.

背景：微生物之间的交流是一个基本的生物学问题。分泌大量代谢物和推定信号分子的丝状真菌是解决此问题的出色模型系统。化学梯度感应和细胞极性调节之间的联系仅在任何真核系统中才能理解。在Neurospora crassa中，一种未知的化学配体介导趋化相互作用，导致遗传相同细胞的细胞融合。这种自我信号的过程基于将MAK2 MAP激酶级联反对与通信细胞相对的尖端的振荡募集。这两个不同的归巢细胞生理状态的快速交替可能反映了信号传递和反应。目的：我们对振荡MAK2信号传导的机械理解受到了以下事实的阻碍：包括假定的分泌信号及其同源受体，MAP激酶级联的调节剂以及MAK2目标的调节剂，这是未知的。该研究项目的长期目标是对脉动mak2信号传导的机械理解。该提案的具体目标是（i）定义MAK2级联的组件，动力学和调节，以及（ii）表征指导化学营养生长反应的MAK2途径效应子。意义：菌丝融合与较高真核生物的遗传相同细胞之间的细胞融合相媲美，这导致形成多核合胞体。人类生物学的重要例子是肌肉分化过程中的成肌细胞融合，胎盘发育过程中的滋养细胞融合以及骨形成过程中的破骨细胞融合。因此，真菌的自给信号为理解更复杂的生物体中细胞通信的分子机制提供了有用的模型。此外，通过共享单个细胞的营养和细胞器，细胞间通信和体细胞融合对于真菌菌落的建立和功能至关重要。因此，菌丝吻合对于致病真菌的宿主定植和毒力也至关重要。理解这一过程将对我们在这种情况下抑制这种过程的能力有重大影响，或者在需要有益的生长时抑制它，或者在这种情况下增强它。