875 research outputs found
How to build a fungal fruit body: from uniform cells to specialized tissue
No full textIt is a challenge in biology to explore the molecular and cellular mechanisms necessary to form a complex three-dimensional structure composed of different cell types. Interesting models to study the underlying processes are fungi that can transform their wire-like hyphal filaments into complex and sometimes container-like fruit bodies. In the past, the role of developmental triggers and transcription factors was a major focus of research on fungal model organisms. In this issue of Molecular Microbiology, Nowrousian and collaborators report that fruit body development of the model organism Sordaria macrospora includes a novel player, a specific membrane protein of the endoplasmic reticulum that is not required for vegetative growth. This finding represents an important step towards connecting regulation of development with the co-ordinated changes in cellular compartments
Deletion of Aspergillus nidulans aroC using a novel blaster module that combines ET cloning and marker rescue
No full textBlaster cassettes are of significant value in functional genomics, as they represent tools with which to inactivate duplicated or homologous genes in an individual organism. We have constructed a novel blaster module which allows repeated gene deletion in the filamentous fungus Aspergillus nidulans. Because bacterial resistance marker cassettes are employed as flanking repeats in direct orientation, the blaster cassette is suited for recombinogenic engineering by ET cloning in Escherichia coli. The functionality of the blaster module was demonstrated by deleting the chorismate mutase-encoding gene aroC of A. nidulans, followed by marker rescue based on mitotic recombination. The resulting aroCDelta strains are auxotrophic for phenylalanine but not tyrosine, and display a limited capacity for fruit body formation and ascosporogenesis, which depends on the phenylalanine/tyrosine supply. The data support the notion that amino acid status has a strong impact on cleistothecium development in A. nidulans
Nitrogen metabolism ofAspergillusand its role in pathogenicity
No full textAspergilli represent unique pathogens. Based on their saprophytic life style they are able to colonize a variety of ecological niches, among them the immunocompromised individual. Distinct fungal attributes that play a role in pathogenicity of aspergilli have been described, and primary metabolism indisputably has to be taken into account for contributing to the virulence potential of this fungal genus. Here we present an overview of studies that focus on this aspect of nutritional versatility In the predominant pathogenic representative Aspergillus fumigatus regulation of nitrogen utilization and sensing of nitrogen sources have been scrutinized with respect to pathogenicity. The impact of distinct metabolic pathways on virulence capacities could be evaluated by inspection of auxotrophic mutant strains. Among them, para-aminobenzoic acid-requiring mutants revealed that this biosynthetic route is strictly required for pathogenicity. For amino acid anabolism only lysine biosynthesis has been investigated in this regard. Fungal amino acid biosynthesis is generally subject to strict regulation mediated by the Cross-Pathway Control system, a conserved regulatory circuit evolved to counteract conditions of nutritional stress. A clear influence of the system on pathogenicity could be observed by targeting its transcriptional activator CpcA. However, additional metabolic characteristics as well as regulatory instruments that compensate environmental challenges need to be addressed in future research with the aim to assess the significance of fungal primary metabolism for pathogenicity of aspergillus species
Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast
No full textThe budding yeast Saccharomyces cerevisiae represents an established model system to study the molecular mechanisms associated to neurodegenerative disorders. A key-feature of Parkinson’s disease is the formation of Lewy bodies, which are cytoplasmic protein inclusions. Misfolded α-synuclein is one of their main constituents. Expression of α-synuclein protein in yeast leads to protein aggregation and cellular toxicity, which is reminiscent to Lewy body containing human cells. The molecular mechanism involved in clearance of α-synuclein aggregates is a central question for elucidating the α-synuclein-related toxicity. Cellular clearance mechanisms include ubiquitin mediated 26S proteasome function as well as lysosome/vacuole associated degradative pathways as autophagy. Various modifications change α-synuclein posttranslationally and alter its inclusion formation, cytotoxicity and the distribution to different clearance pathways. Several of these modification sites are conserved from yeast to human. In this review, we summarize recent findings on the effect of phosphorylation and sumoylation of α-synuclein to the enhanced channeling to either the autophagy or the proteasome degradation pathway in yeast model of Parkinson’s disease
Controlling transcription by destruction: the regulation of yeast Gcn4p stability
No full textThe Gcn4 protein, a member of the AP-1 family of transcription factors, is involved in the expression of more than 500 genes in the budding yeast Saccharomyces cerevisiae. A key role of Gcn4p is the increased expression of many amino acid biosynthesis genes in response to amino acid starvation. The accumulation of this transcription activator is mainly induced by efficient translation of the GCN4 ORF and by stabilisation of the Gcn4 protein. Under normal growth conditions, Gcn4p is a highly unstable protein, thereby resembling many eukaryotic transcription factors, including mammalian Jun and Myc proteins. Gcn4p is degraded by ubiquitin-dependent proteolysis mediated by the Skp1/cullin/F-box (SCF) ubiquitin ligase, which recognises specifically phosphorylated substrates. Two cyclin-dependent protein kinases, Pho85p and Srb10p, have crucial functions in regulating Gcn4p phosphorylation and degradation. The past few years have revealed many novel insights into these regulatory processes. Here, we summarise current knowledge about the factors and mechanisms regulating Gcn4p stability
Manipulation of fungal development as source of novel secondary metabolites for biotechnology
Get PDFFungal genomics revealed a large potential of yet-unexplored secondary metabolites, which are not produced during vegetative growth. The discovery of novel bioactive compounds is increasingly gaining importance. The high number of resistances against established antibiotics requires novel drugs to counteract increasing human and animal mortality rates. In addition, growth of plant pathogens has to be controlled to minimize harvest losses. An additional critical issue is the post-harvest production of deleterious mycotoxins. Fungal development and secondary metabolite production are linked processes. Therefore, molecular regulators of development might be suitable to discover new bioactive fungal molecules or to serve as targets to control fungal growth, development, or secondary metabolite production. The fungal impact is relevant as well for our healthcare systems as for agriculture. We propose here to use the knowledge about mutant strains discovered in fungal model systems for a broader application to detect and explore new fungal drugs or toxins. As examples, mutant strains impaired in two conserved eukaryotic regulatory complexes are discussed. The COP9 signalosome (CSN) and the velvet complex act at the interface between development and secondary metabolism. The CSN is a multi-protein complex of up to eight subunits and controls the activation of CULLIN-RING E3 ubiquitin ligases, which mark substrates with ubiquitin chains for protein degradation by the proteasome. The nuclear velvet complex consists of the velvet-domain proteins VeA and VelB and the putative methyltransferase LaeA acting as a global regulator for secondary metabolism. Defects in both complexes disturb fungal development, light perception, and the control of secondary metabolism. The potential biotechnological relevance of these developmental fungal mutant strains for drug discovery, agriculture, food safety, and human healthcare is discussed.Deutsche Forschungsgemeinschaft (DFG) [SFB860, SPP1365, BR1502/11
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