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TitleIdentification of metabolic pathways influenced by the G-protein coupled receptors GprB and GprD in Aspergillus nidulans
Author(s)de Souza, Wagner R
Morais, Enyara Rezende
Krohn, Nadia Graciele
Savoldi, Marcela
Goldman, Maria Helena S
Rodrigues, Fernando
Caldana, Camila
Semelka, Charles T
Tikunov, Andrey P
Macdonald, Jeffrey M
Goldman, Gustavo Henrique
KeywordsAspergillus nidulans
Carbohydrate Metabolism
Culture Media
Cyclic AMP-Dependent Protein Kinases
Fungal Proteins
Gene Expression Regulation, Fungal
Gene Knockout Techniques
Heterotrimeric GTP-Binding Proteins
Multigene Family
Protein Transport
Receptors, G-Protein-Coupled
Signal Transduction
Metabolic Networks and Pathways
Issue date2013
PublisherPublic Library of Science (PLOS)
JournalPLoS ONE
Citationde Souza WR, Morais ER, Krohn NG, Savoldi M, Goldman MHS, Rodrigues F, et al. (2013) Identification of Metabolic Pathways Influenced by the G-Protein Coupled Receptors GprB and GprD in Aspergillus nidulans. PLoS ONE 8(5): e62088.
Abstract(s)Heterotrimeric G-protein-mediated signaling pathways play a pivotal role in transmembrane signaling in eukaryotes. Our main aim was to identify signaling pathways regulated by A. nidulans GprB and GprD G-protein coupled receptors (GPCRs). When these two null mutant strains were compared to the wild-type strain, the ΔgprB mutant showed an increased protein kinase A (PKA) activity while growing in glucose 1% and during starvation. In contrast, the ΔgprD has a much lower PKA activity upon starvation. Transcriptomics and (1)H NMR-based metabolomics were performed on two single null mutants grown on glucose. We noted modulation in the expression of 11 secondary metabolism gene clusters when the ΔgprB and ΔgprD mutant strains were grown in 1% glucose. Several members of the sterigmatocystin-aflatoxin gene cluster presented down-regulation in both mutant strains. The genes of the NR-PKS monodictyphenone biosynthesis cluster had overall increased mRNA accumulation in ΔgprB, while in the ΔgprD mutant strain the genes had decreased mRNA accumulation. Principal component analysis of the metabolomic data demonstrated that there was a significant metabolite shift in the ΔgprD strain. The (1)H NMR analysis revealed significant expression of essential amino acids with elevated levels in the ΔgprD strain, compared to the wild-type and ΔgprB strains. With the results, we demonstrated the differential expression of a variety of genes related mainly to secondary metabolism, sexual development, stress signaling, and amino acid metabolism. We propose that the absence of GPCRs triggered stress responses at the genetic level. The data suggested an intimate relationship among different G-protein coupled receptors, fine-tune regulation of secondary and amino acid metabolisms, and fungal development.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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