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Analysis of the regulatory function of amino acids on metabolic targets and serotonin production in Drosophila melanogaster

dc.contributor.advisorPankratz, Michael
dc.contributor.authorHübner, Tatjana
dc.date.accessioned2020-04-22T20:51:02Z
dc.date.available2020-04-22T20:51:02Z
dc.date.issued09.08.2016
dc.identifier.urihttp://hdl.handle.net/20.500.11811/6851
dc.description.abstractAmino acid sensing mediates metabolic and behavioural adjustments in response to organismal needs. Several pathways are believed to be involved in amino acid sensing, including the TOR (Target of Rapamycin) pathway. However, the mechanism of how organisms adjust their metabolism and feeding behaviour to their internal amino acid status is still not well understood.
In this instance, the model organism Drosophila melanogaster was used to investigate whether the amino acid transporter Pathetic (Path), which signals amino acid availability to the TOR pathway, is involved in metabolic and neuronal adjustment to nutritional status. Transcriptional analysis of the gene target of brain insulin (tobi) demonstrated a metabolic adjustment to amino acid availability, where the transcript level of tobi was dependent on nutritional peptide and amino acid composition. tobi transcript levels could also be modulated by the overexpression of the amino acid transporter Pathetic. A high level of pathetic expression was detected in serotonergic neurons, which are involved in the regulation of feeding behaviour and starvation resistance. Overexpression of Pathetic in these neurons led to an increase of the serotonin producing enzyme Tryptophan hydroxylase in the larval brain, decreased the expression of the starvation marker lipase3, and reduced survival after pupation. This indicates that in Drosophila larvae, Pathetic expression in serotonergic neurons affects serotonin signalling.
In adult Drosophila melanogaster, serotonin signalling in the insulin producing cells (IPC’s) modulates insulin signalling and starvation resistance: a decrease in serotonin signalling increases insulin-like peptide availability and decreases starvation resistance. An adjustment of insulin signalling in Drosophila is essential for starvation resistance. The transcript level of the insulin receptor (InR) indicates an adjustment to increased insulin signalling by a negative feedback mechanism.
Transcriptional analysis of InR upon Path overexpression in serotonergic neurons revealed an increase of insulin signalling in adult Drosophila. Starvation analysis of adult Drosophila melanogaster showed a decrease of starvation resistance. These results suggest a decrease in serotonin signalling in the IPC’s. The induction of TOR pathway in serotonergic neurons via overexpression of the TOR activator Rheb (Ras homolog enriched in brain) lead to a similar effect, but could not induce insulin signalling to the extent of as Path overexpression. The results of this work showed that increased expression of the transporter Pathetic modulates the expression of metabolic target genes and enzymes involved in serotonin production, and also affects serotonin signalling in the adult Drosophila melanogaster brain. Therefore, the TOR pathway might be involved in the regulation of metabolic and behavioural adjustment to the organismal nutrient status via the transporter Pathetic.
dc.language.isoeng
dc.rightsIn Copyright
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectTOR-Signalweg
dc.subjectSerotonin
dc.subjectAminosäure
dc.subjectTransporter
dc.subjectNährstoffsignale
dc.subjectNeurotransmitter
dc.subjectTOR pathway
dc.subjectamino acid
dc.subjectnutrient signalling
dc.subject.ddc570 Biowissenschaften, Biologie
dc.titleAnalysis of the regulatory function of amino acids on metabolic targets and serotonin production in Drosophila melanogaster
dc.typeDissertation oder Habilitation
dc.publisher.nameUniversitäts- und Landesbibliothek Bonn
dc.publisher.locationBonn
dc.rights.accessRightsopenAccess
dc.identifier.urnhttps://nbn-resolving.org/urn:nbn:de:hbz:5n-44279
ulbbn.pubtypeErstveröffentlichung
ulbbnediss.affiliation.nameRheinische Friedrich-Wilhelms-Universität Bonn
ulbbnediss.affiliation.locationBonn
ulbbnediss.thesis.levelDissertation
ulbbnediss.dissID4427
ulbbnediss.date.accepted2015-12-09
ulbbnediss.instituteMathematisch-Naturwissenschaftliche Fakultät : Fachgruppe Molekulare Biomedizin / Life & Medical Sciences-Institut (LIMES)
ulbbnediss.fakultaetMathematisch-Naturwissenschaftliche Fakultät
dc.contributor.coRefereeBauer, Reinhard


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