8 research outputs found

    The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast

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    The detection and amplification of extracellular signals requires the involvement of multiple protein components. In mammalian cells the receptor of activated C kinase (RACK1) is an important scaffolding protein for signal transduction networks. Further, it also performs a critical function in regulating the cell cycle by modulating the G1/S transition. Many eukaryotic cells express RACK1 orthologs, with one example being Cpc2p in the fission yeast Schizosaccharomyces pombe. In contrast to RACK1, Cpc2p has been described to positively regulate, at the ribosomal level, cells entry into M phase. In addition, Cpc2p controls the stress response pathways through an interaction with Msa2p, and sexual development by modulating Ran1p/Pat1p. Here we describe investigations into the role, which Cpc2p performs in controlling the G protein-mediated mating response pathway. Despite structural similarity to Gβ-like subunits, Cpc2p appears not to function at the G protein level. However, upon pheromone stimulation, cells overexpressing Cpc2p display substantial cell morphology defects, disorientation of septum formation and a significantly protracted G1 arrest. Cpc2p has the potential to function at multiple positions within the pheromone response pathway. We provide a mechanistic interpretation of this novel data by linking Cpc2p function, during the mating response, with its previous described interactions with Ran1p/Pat1p. We suggest that overexpressing Cpc2p prolongs the stimulated state of pheromone-induced cells by increasing ste11 gene expression. These data indicate that Cpc2p regulates the pheromone-induced cell cycle arrest in fission yeast by delaying cells entry into S phase

    Role of the RNA-Binding Protein Nrd1 in Stress Granule Formation and Its Implication in the Stress Response in Fission Yeast

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    We have previously identified the RNA recognition motif (RRM)-type RNA-binding protein Nrd1 as an important regulator of the posttranscriptional expression of myosin in fission yeast. Pmk1 MAPK-dependent phosphorylation negatively regulates the RNA-binding activity of Nrd1. Here, we report the role of Nrd1 in stress-induced RNA granules. Nrd1 can localize to poly(A)-binding protein (Pabp)-positive RNA granules in response to various stress stimuli, including heat shock, arsenite treatment, and oxidative stress. Interestingly, compared with the unphosphorylatable Nrd1, Nrd1DD (phosphorylation-mimic version of Nrd1) translocates more quickly from the cytoplasm to the stress granules in response to various stimuli; this suggests that the phosphorylation of Nrd1 by MAPK enhances its localization to stress-induced cytoplasmic granules. Nrd1 binds to Cpc2 (fission yeast RACK) in a phosphorylation-dependent manner and deletion of Cpc2 affects the formation of Nrd1-positive granules upon arsenite treatment. Moreover, the depletion of Nrd1 leads to a delay in Pabp-positive RNA granule formation, and overexpression of Nrd1 results in an increased size and number of Pabp-positive granules. Interestingly, Nrd1 deletion induced resistance to sustained stresses and enhanced sensitivity to transient stresses. In conclusion, our results indicate that Nrd1 plays a role in stress-induced granule formation, which affects stress resistance in fission yeast

    The influence of wasabi on the gut microbiota of high-carbohydrate, high-fat diet-induced hypertensive Wistar rats

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    The human gut microbiota plays a critical role in the regulation of adiposity, obesity and metabolic and cardiovascular disease. Wasabi is a pungent spice and its active component, allyl isothiocyanate, improves plasma triacylglycerol, cholesterol and high blood pressure in rodents, but it is unclear if this occurs through alterations to the composition of the microbiota. The aim of this study was to determine the effectiveness of Wasabi japonica stem and rhizome blend on ameliorating cardiovascular disease parameters including plasma sodium concentration, systolic blood pressure (SBP), plasma endothelin-1 and angiotensin II concentrations by altering the gut microbiota in a Wistar rat model of obesity and metabolic syndrome. Rats were randomized to receive a corn starch or high-carbohydrate/high-fat diet for 8 weeks before being allocated to supplementation with wasabi powder (5% (w/w) in food) or not for an additional 8 weeks. At the end of the trial, rats were grouped according to blood pressure status. Wasabi supplementation prevented the development of hypertension and was also associated with significantly increased abundance of Allobaculum, Sutterella, Uncl. S247, Uncl. Coriobacteriaceae and Bifidobacterium. Hypertension was positively correlated with higher abundance of Oscillospira, Uncl. Lachnospiraceae and Uncl. Clostridiales, Uncl. Bacteroidales and Butyricimonas. Oscillospira and Butyricimonas abundances were specifically positively correlated with systolic blood pressure. Overall, the improved host cardiovascular health in diet-induced obese rats supplemented with wasabi powder may involve changes to the gut microbiota composition

    Activation of AMPK by Medicinal Plants and Natural Products: Its Role in Type 2 Diabetes Mellitus

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