Components, dynamics and effectors of the MAK2 MAP kinase cascade

• Applicant: Privatdozent Dr. Stephan Seiler
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258036129

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.

• DFG Programme: Research Grants