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A novel role for polysaccharide monooxygenases in signaling, chemotropic interactions and cell fusion


It has been estimated that up to one quarter of the world's biomass is of fungal origin, comprising approximately six million species. To interact with one another and respond to environmental cues, these species communicate and respond via chemical languages. In filamentous ascomycete fungi, the formation of an interconnected, multinucleate hyphal network is constructed via communication and fusion of germinated asexual spores (germlings) and hyphae. In nature, filamentous fungi play important roles in decomposition of plant and animal matter, nutrient cycling and nutrient transport in the hyphal network, including an association with plants, both as symbionts and as pathogens. This project defines a new biological function during hyphal network formation for a class of oxidative enzymes, termed polysaccharide monooxygenases (PMOs), that play a role during signaling, chemotropic interactions and cell wall remodeling during somatic cell fusion in filamentous fungi. Previously, this class of enzymes has only been associated with extracellular degradative capacities, providing a paradigm shift in the cellular function of this class of proteins. The discovery of a role for copper-dependent PMOs in cell signaling, along with the characterization of new substrates for these enzymes, will greatly impact this field of research; genes encoding PMOs have been found in human and plant pathogens and may also be involved in symbiotic relationships. This project brings expertise on cell signaling, cell biology and genetics with deep expertise in biochemistry and structural biology on PMOs, and provides an excellent training opportunity for undergraduate, graduate students and postdoctoral associates. Workshops will be developed on the use of the filamentous fungus Neurospora crassa to identify and characterize molecular players involved in cell-cell communication and fusion in collaboration with educational science organizations and will form the basis of an intensive three-week undergraduate course at the University of California - Berkeley. Live cell imaging movies from this project and others will enrich educational aspects on the role of fungi in the environment in exhibitions provided by the Mycological Society of San Francisco and the Bay Area Mycological Society. <br/> <br/>Chemotropic interactions between fungal germlings (or hyphae in a colony), initiates cell communication, followed by a switch from cell growth to cell wall breakdown and membrane merger at the contact point between adhered cells. A role for a predicted PMO, HAM-7, is required for chemotropic interactions and functions through the cell wall integrity (CWI) MAP kinase signaling pathway in filamentous fungi. Strains lacking ham-7 fail to undergo cell fusion and thus lack an interconnected hyphal network. The ham-7 gene and its relatives form a unique clade among PMOs in fungi. The substrate for the HAM-7 PMO is currently unknown and defining the activity of HAM-7, its substrate and role in chemotropic interactions and cell fusion using biochemical methods, structural biology, cell biology and genetics is a major objective of this project. A second PMO, CWR-1, which is predicted to use chitin as a substrate based on homology, functions as a negative regulator of the switch from cell growth to cell wall disassembly during cell fusion. A predicted membrane protein, CWR-3 is required for CWR-1 to function in cell wall disassembly, suggesting it may function as a receptor for the product of the CWR-1 enzymatic activity. This project will link the function of polysaccharide monooxygenases oxidative capacity with the enigmatic properties of chemical languages involved in germling/hyphal communication that dictates the behavior of cells seeking to undergo vegetative fusion with their own kind. The work described in this project will be transformative in defining new biological roles for this class of enzymes/proteins that may be broadly applicable to both eukaryotic and prokaryotic species that encode PMOs in their genomes.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Michael Marletta; Glass, Louise
University of California - Berkeley
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