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。丝状真菌可以分泌大量的代谢物和假定的信号分子，是解决这一问题的优秀模型系统。在任何真核系统中，人们对化学梯度感应和细胞极性调节之间的联系知之甚少。在粗糙脉孢菌中，一种未知的化学配体介导趋化相互作用，导致遗传上相同的细胞的细胞融合。这种自我信号传递的过程是基于MAK2蛋白激酶级联到通讯细胞的相反尖端的振荡募集。归巢细胞这两种不同生理状态的快速变化可能反映了信号传递和反应。目的：我们对振荡MAK2信号机制的理解受到这样一个事实的阻碍，即信号机制的大多数组成部分，包括一个假定的分泌信号及其同源受体，MAP激酶级联的调节因子以及MAK2靶标，都是未知的。这一研究项目的长期目标是从机制上理解脉动性MAK2信号。该提案的具体目标是(I)定义MAK2级联的组成、动力学和调节，以及(Ii)表征指导化学营养生长反应的MAK2途径效应器。意义：菌丝融合相当于高等真核生物中遗传相同的细胞之间的细胞融合，这会导致多核合胞体的形成。人类生物学的重要例子包括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，真菌自身信号传递为理解更复杂生物体中细胞通讯的分子机制提供了一个有用的模型。此外，通过共享单个细胞的营养物质和细胞器，细胞间的通讯和体细胞融合对真菌菌落的建立和功能至关重要。因此，菌丝融合对寄主定植和病原真菌的毒力也是至关重要的。理解这一过程将对我们干预这一过程的能力产生重大影响，无论是在有害真菌的情况下抑制它，还是在有益的生长需要时增强它。