title: Identification of metabolic pathways influenced by the G-protein coupled receptors GprB and GprD in Aspergillus nidulans.
abstract: 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.
authors: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors: Wagner R
authors: WR
authors: de Souza
authors: Enyara Rezende
authors: ER
authors: Morais
authors: Nadia Graciele
authors: NG
authors: Krohn
authors: Marcela
authors: M
authors: Savoldi
authors: Maria Helena S
authors: MH
authors: Goldman
authors: Fernando
authors: F
authors: Rodrigues
authors: Camila
authors: C
authors: Caldana
authors: Charles T
authors: CT
authors: Semelka
authors: Andrey P
authors: AP
authors: Tikunov
authors: Jeffrey M
authors: JM
authors: Macdonald
authors: Gustavo Henrique
authors: GH
authors: Goldman
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D003470:Culture Media; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D005810:Multigene Family; D010641:Phenotype; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D003470:Culture Media; D005656:Fungal Proteins; D043562:Receptors, G-Protein-Coupled; D017868:Cyclic AMP-Dependent Protein Kinases; D020962:Heterotrimeric GTP-Binding Proteins; D005947:Glucose
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