Identifying Natural Products (NPs) as potential UPR inhibitors for crop protection

As far as the future of agriculture is concerned, one major challenge will be to face an expected increase in health risks due to pesticides together with a lower efficiency of crop treatments. Therefore it is today necessary to develop new strategies to enhance the effectiveness and sustainability of current control methods. The so-called “Alternaria Leaf Spot“ is a common disease of crucifers caused by the fungal pathogen Alternaria brassicicola which affects different crops including cabbage, kale, Brussels sprout, cauliflower and broccoli. Indole phytoalexins camalexin and brassinin play in planta a key role in crop protection against this necrotrophic agent. However it has been shown that mutants become phytoalexin-resistant by activating at least three signaling pathways named as Cell Wall Integrity (CWI), High Osmolarity Glycerol (HOG) and Unfolded Protein Response (UPR) [1,2]. The latter is particularly involved in the fungus protection against phytoalexins since UPR deficient avirulent mutants of A. brassicicola appear as hypersensitive to camalexin and brassinin [3]. Since very few UPR inhibitors such as the synthetic STF-083010 [4] are known we decided to develop an original screening assay, detecting the production of a HAC1 fluorescence-induced protein, i.e. a transcriptional activator involved in the UPR pathway, in Saccharomyces cerevisiae cultures (Figure 1). The preliminary screening of an in-house NPs library [c.a. 70 compounds (polyphenols, terpenoids and alkaloids)] clearly revealed aescin (Aesculus hippocastanum)] as a potential UPR inhibitor

Nucleocytoplasmic transport : signals, mechanisms and regulation

In eukaryotic organisms, DNA replication and RNA biogenesis occur in the cell nucleus, whereas protein synthesis occurs in the cytoplasm. Integration of these activities depends on selective transport of proteins and ribonucleoprotein particles between the two compartments. Transport across the nuclear envelope occurs through large multiprotein structures, termed nuclear pore complexes. It is signal-mediated and requires both energy and soluble factors, including shuttling carriers. Here I summarize current understanding of nucleocytoplasmic transport and illustrate the importance of regulated transport for signal transduction