Validamycin A enhances the interaction between neutral trehalase and 14‑3‑3 protein Bmh1 in Fusarium graminearum

2021 ◽  
Author(s):  
Li Ren ◽  
Yi-Ping Hou ◽  
Yuanye Zhu ◽  
Fei-Fei Zhao ◽  
Yabing Duan ◽  
...  

Trehalase is considered the main target of the biological fungicide validamycin A, and toxicology mechanism of validamycin A is unknown. 14-3-3 proteins, highly conserved proteins, participate in diverse cellular processes, including enzyme activation, protein localization and molecular chaperone. In Saccharomyces cerevisiae, the 14-3-3 protein Bmh1could interact with Nth1 to respond specific external stimuli. Here, we characterized FgNth, FgBmh1, and FgBmh2 in Fusarium graminearum. ΔFgNth, ΔFgBmh1, and ΔFgBmh2 displayed great growth defects when compared to wild-type PH-1. When exposed to validamycin A, high osmotic and high temperature stresses, ΔFgNth, ΔFgBmh1, and ΔFgBmh2 showed more tolerance than WT. Both ΔFgNth and ΔFgBmh1 displayed reduced deoxynivalenol (DON) production but opposite for ΔFgBmh2, and all three deletion mutants showed reduced virulence on wheat coleoptiles. In addition, Co-immunoprecipitation (Co-IP) experiments suggested that FgBmh1 and FgBmh2 both interact with FgNth, but no interaction was detected between FgBmh1 and FgBmh2 in our experiments. Further, validamycin A enhances the interaction between FgBmh1 and FgNth in a positive correlation under concentrations of 1-100μg/mL. Besides, both high osmotic and high temperature stresses promote the interaction between FgBmh1 and FgNth. Co-IP assay also showed that neither FgBmh1 nor FgBmh2 could interact with FgPbs2, a MAPKK kinase in the high-osmolarity glycerol (HOG) pathway. However, FgBmh2 but not FgBmh1 binds to the heat shock protein FgHsp70 in F. graminearum. Taken together, our results demonstrate that FgNth and FgBmhs are involved in growth, responces to external stresses and virulence, and validamycin A enhanced the interaction between FgNth and FgBmh1in F. graminearum.

2009 ◽  
Vol 34 (12) ◽  
pp. 2196-2201 ◽  
Author(s):  
Xue-Li QI ◽  
Lin HU ◽  
Hai-Bin DONG ◽  
Lei ZHANG ◽  
Gen-Song WANG ◽  
...  

2020 ◽  
Vol 48 (18) ◽  
pp. 10015-10033 ◽  
Author(s):  
Lisa Aberle ◽  
Annika Krüger ◽  
Julia M Reber ◽  
Michelle Lippmann ◽  
Matthias Hufnagel ◽  
...  

Abstract Poly(ADP-ribosyl)ation regulates numerous cellular processes like genome maintenance and cell death, thus providing protective functions but also contributing to several pathological conditions. Poly(ADP-ribose) (PAR) molecules exhibit a remarkable heterogeneity in chain lengths and branching frequencies, but the biological significance of this is basically unknown. To unravel structure-specific functions of PAR, we used PARP1 mutants producing PAR of different qualities, i.e. short and hypobranched (PARP1\G972R), short and moderately hyperbranched (PARP1\Y986S), or strongly hyperbranched PAR (PARP1\Y986H). By reconstituting HeLa PARP1 knockout cells, we demonstrate that PARP1\G972R negatively affects cellular endpoints, such as viability, cell cycle progression and genotoxic stress resistance. In contrast, PARP1\Y986S elicits only mild effects, suggesting that PAR branching compensates for short polymer length. Interestingly, PARP1\Y986H exhibits moderate beneficial effects on cell physiology. Furthermore, different PARP1 mutants have distinct effects on molecular processes, such as gene expression and protein localization dynamics of PARP1 itself, and of its downstream factor XRCC1. Finally, the biological relevance of PAR branching is emphasized by the fact that branching frequencies vary considerably during different phases of the DNA damage-induced PARylation reaction and between different mouse tissues. Taken together, this study reveals that PAR branching and chain length essentially affect cellular functions, which further supports the notion of a ‘PAR code’.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Qiongshan Wang ◽  
Nian Liu ◽  
Xiyan Yang ◽  
Lili Tu ◽  
Xianlong Zhang

2014 ◽  
Vol 58 (4) ◽  
pp. 2089-2097 ◽  
Author(s):  
Lee W. Goneau ◽  
Nigel S. Yeoh ◽  
Kyle W. MacDonald ◽  
Peter A. Cadieux ◽  
Jeremy P. Burton ◽  
...  

ABSTRACTPersister cells represent a multidrug-tolerant (MDT), physiologically distinct subpopulation of bacteria. The ability of these organisms to survive lethal antibiotic doses raises concern over their potential role in chronic disease, such as recurrent urinary tract infection (RUTI). Persistence is believed to be conveyed through global metabolic dormancy, which yields organisms unresponsive to external stimuli. However, recent studies have contested this stance. Here, various antibiotics that target different cellular processes were used to dissect the activity of transcription, translation, and peptidoglycan turnover in persister cells. Differential susceptibility patterns were found in type I and type II persisters, and responses differed betweenStaphylococcus saprophyticusandEscherichia coliuropathogens. Further, SOS-deficient strains were sensitized to ciprofloxacin, suggesting DNA gyrase activity in persisters and indicating the importance of active DNA repair systems for ciprofloxacin tolerance. These results indicate that global dormancyper secannot sufficiently account for antibiotic tolerance. Rather, the activity of individual cellular processes dictates multidrug tolerance in an antibiotic-specific fashion. Furthermore, the susceptibility patterns of persisters depended on their mechanisms of onset, with subinhibitory antibiotic pretreatments selectively shutting down cognate targets and increasing the persister fraction against the same agent. Interestingly, antibiotics targeting transcription and translation enhanced persistence against multiple agents indirectly related to these processes. Conducting these assays with uropathogenicE. coliisolated from RUTI patients revealed an enriched persister fraction compared to organisms cleared with standard antibiotic therapy. This finding suggests that persister traits are either selected for during prolonged antibiotic treatment or initially contribute to therapy failure.


2022 ◽  
Vol 4 (1) ◽  
Author(s):  
Yu Wang ◽  
Nan Yang ◽  
Yunna Zheng ◽  
Jiaolin Yue ◽  
Vijai Bhadauria ◽  
...  

AbstractUbiquitination is a vital protein post-translational modification (PTM) prevalent in eukaryotes. This modification regulates multiple cellular processes through protein degradation mediated by the 26S proteasome or affecting protein–protein interaction and protein localization. Magnaporthe oryzae causes rice blast disease, which is one of the most devastating crop diseases worldwide. In M. oryzae, ubiquitination plays important roles in growth, pathogenicity, stress response and effector-mediated plant-pathogen interaction. In this review, we summarize the roles of ubiquitination components in the above biological processes of M. oryzae, including single- or multi-subunit E3s, E2s, components of 26S proteasome and also deubiquitinating enzymes. The essential function of ubiquitination in plant-fungus interaction is also discussed. Moreover, this review presents several issues related to the ubiquitination system in M. oryzae, which need to be further explored in future researches.


2018 ◽  
Vol 31 (11) ◽  
pp. 1121-1133 ◽  
Author(s):  
Zunyong Liu ◽  
Na Liu ◽  
Huixian Jiang ◽  
Leiyan Yan ◽  
Zhonghua Ma ◽  
...  

The type 2A protein phosphatases (PP2As) are holoenzymes in all eukaryotes but their activators remain unknown in filamentous fungi. Fusarium graminearum contains three PP2As (FgPp2A, FgSit4, and FgPpg1), which play critical roles in fungal growth, development, and virulence. Here, we identified two PP2A activators (PTPAs), FgRrd1 and FgRrd2, and found that they control PP2A activity in a PP2A-specific manner. FgRrd1 interacts with FgPpg1, but FgRrd2 interacts with FgPp2A and very weakly with FgSit4. Furthermore, FgRrd2 activates FgPp2A via regulating FgPp2A methylation. Phenotypic assays showed that FgRrd1 and FgRrd2 regulate mycelial growth, conidiation, sexual development, and lipid droplet biogenesis. More importantly, both FgRrd1 and FgRrd2 interact with RNA polymerase II, subsequently modulating its enrichments at the promoters of mycotoxin biosynthesis genes, which is independent on PP2A. In addition, FgRrd2 modulates response to phenylpyrrole fungicide, via regulating the phosphorylation of kinase FgHog1 in the high-osmolarity glycerol pathway, and to caffeine, via modulating FgPp2A methylation. Taken together, results of this study indicate that FgRrd1 and FgRrd2 regulate multiple physiological processes via different regulatory mechanisms in F. graminearum, which provides a novel insight into understanding the biological functions of PTPAs in fungi.


2021 ◽  
Author(s):  
Swetha Ramadesikan ◽  
Lisette Skiba ◽  
Jennifer Lee ◽  
Kayalvizhi Madhivanan ◽  
Daipayan Sarkar ◽  
...  

Abstract Lowe Syndrome (LS) is a lethal genetic disorder caused by mutations in the OCRL1 gene which encodes the lipid 5′ phosphatase Ocrl1. Patients exhibit a characteristic triad of symptoms including eye, brain and kidney abnormalities with renal failure as the most common cause of premature death. Over 200 OCRL1 mutations have been identified in LS, but their specific impact on cellular processes is unknown. Despite observations of heterogeneity in patient symptom severity, there is little understanding of the correlation between genotype and its impact on phenotype. Here, we show that different mutations had diverse effects on protein localization and on triggering LS cellular phenotypes. In addition, some mutations affecting specific domains imparted unique characteristics to the resulting mutated protein. We also propose that certain mutations conformationally affect the 5′-phosphatase domain of the protein, resulting in loss of enzymatic activity and causing common and specific phenotypes (a conformational disease scenario). This study is the first to show the differential effect of patient 5′-phosphatase mutations on cellular phenotypes and introduces a conformational disease component in LS. This work provides a framework that explains symptom heterogeneity and can help stratify patients as well as to produce a more accurate prognosis depending on the nature and location of the mutation within the OCRL1 gene.


2021 ◽  
Author(s):  
Peng Zhu ◽  
Jennifer Burney

Abstract. Irrigation has important implications for sustaining global food production, enabling crop water demand to be met even under dry conditions. Added water also cools crop plants through transpiration; irrigation might thus play an important role in a warmer climate by simultaneously moderating water and high temperature stresses. Here we use satellite-derived evapotranspiration estimates, land surface temperature (LST) measurements, and crop phenological stage information from Nebraska maize to quantify how irrigation relieves both water and temperature stresses. Our study shows that, unlike air temperature metrics, satellite-derived LST detects significant irrigation-induced cooling effect, especially during the grain filling period (GFP) of crop growth. This cooling is likely to extend the maize growing season, especially for GFP, likely due to the stronger temperature sensitivity of phenological development during this stage. The analysis also suggests that irrigation not only reduces water and temperature stress but also weakens the response of yield to these stresses. Specifically, temperature stress is significantly weakened for reproductive processes in irrigated crops. The attribution analysis further suggests that water and high temperature stress alleviation contributes to 65 % and 35 % of yield benefit, respectively. Our study underlines the relative importance of high temperature stress alleviation in yield improvement and the necessity of simulating crop surface temperature to better quantify heat stress effects in crop yield models. Finally, untangling irrigation effects on both heat and water stress mitigation has important implications for designing agricultural adaptation strategies under climate change.


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