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Xenopus laevis tolerate dehydration when their environments evaporate during summer months. Protein phosphorylation has previously shown to regulate important adaptations in X. laevis, including the transition to anaerobic metabolism. We therefore performed phosphoproteomic analysis of X. laevis to further elucidate the cellular and metabolic responses to dehydration. Phosphoproteins were enriched in cellular functions and pathways related to glycolysis/gluconeogenesis, the TCA cycle, and protein metabolism, among others. The prominence of phosphoproteins related to glucose metabolism led us to discover that the hypoxia-inducible PFKFB3 enzyme was highly phosphorylated and likely activated during dehydration, a feature of many cancers. Expression of the four transcript variants of the pfkfb3 gene was found all to be upregulated during dehydration, potentially due to the enrichment of hypoxia responsive elements in the pfkfb3 promoter. These results further support the role of anaerobic glycolysis during dehydration in X. laevis and elucidate a potential mechanism for its increased rate.
Figure 1. Hierarchical Clustering Analysis of Phosphopeptides in the Liver and Muscle of Xenopus Laevis in Response to Dehydration.
Clustering was performed on samples from control and dehydrated animals in (A) liver and (B) skeletal muscle. Samples (arranged horizontally) were clustered by Euclidean distance between relative quantities of phosphopeptides, and phosphopeptides (arranged vertically) were clustered based on Euclidean distance between each sample. Colors indicate Z score (standardized quantities) where red is a high Z score and blue is a low Z score. The experimental group the sample belongs to is indicated by blue (control) or red (dehydrated) bars above the heatmap.
Figure 2. Principal Component Analysis of Samples in the Liver and Muscle of Xenopus Laevis in Response to Dehydration
Principle component analysis was performed on phosphopeptide relative quantities in (A) liver, (B) skeletal muscle, and (C) both tissues. The cumulative explained variance of principal components is plotted in (D).
Figure 3. Volcano Plot of Phosphopeptides from Liver and Muscle of Xenopus Laevis in Response to Dehydration.
Phosphopeptides that had significantly increased (FDR-corrected p value < 0.05) and decreased relative abundance in dehydration samples are in blue and red, respectively, for (A) liver and (B) skeletal muscle. Phosphopeptides from liver and skeletal muscle ordered by Log2 fold-change is shown in (C).
Figure 4. Venn Diagram of Phosphoproteins from Liver and Muscle of Xenopus Laevis in Response to Dehydration.
Phosphoproteins with at least one corresponding phosphopeptide identified in liver and/or muscle is shown in (A), whereas only those with at least one significantly differentially abundant phosphopeptides are shown in (B).
Figure 5. Enriched Gene Ontology Biological Processes Semantic Relation Network in the Liver of Xenopus Laevis Exposed to Dehydration.
Enriched GO biological processes terms were summarized by REVIGO (Supek et al., 2011) and resulting semantic relation network was plotted using Cytoscape. Node size is proportional to the number of genes each term encompasses and the darker the blue the lower the FDR-adjusted p value. Edges indicate semantic relationship.
Figure 6. Enriched Gene Ontology Term Semantic Relation Networks in Skeletal Muscle of Xenopus Laevis Exposed to Dehydration.
GO biological processes are in (A), cellular compartments in (B), and molecular functions in (C). All other details are as in Figure 5.
Figure 7. Top Ten Enriched Kyoto Encyclopedia of Genes and Genomes Pathways in the Liver of Xenopus Laevis Exposed to Dehydration.
Terms in dark blue are statistically enriched (FDR-corrected p value < 0.05), terms in light blue are not significantly enriched.
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