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Peptide and GABA regulation of Peptide Hormone Release in the Drosophila Brain
Stockholm University, Faculty of Science, Department of Zoology.
2010 (English)Licentiate thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Department of Zoology, Stockholm University , 2010. , 39 p.
Series
Licentiatavhandling / Zoologiska institutionen, Stockholms universitet, ISSN 1403-5227
National Category
Zoology
Identifiers
URN: urn:nbn:se:su:diva-65831OAI: oai:DiVA.org:su-65831DiVA: diva2:465035
Presentation
2010-12-07, 14:00 (English)
Opponent
Supervisors
Available from: 2013-01-25 Created: 2011-12-14 Last updated: 2014-10-28Bibliographically approved
List of papers
1. Insulin Signaling, Lifespan and Stress Resistance Are Modulated by Metabotropic GABA Receptors on Insulin Producing Cells in the Brain of Drosophila
Open this publication in new window or tab >>Insulin Signaling, Lifespan and Stress Resistance Are Modulated by Metabotropic GABA Receptors on Insulin Producing Cells in the Brain of Drosophila
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2010 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 12, e15780- p.Article in journal (Refereed) Published
Abstract [en]

Insulin-like peptides (ILPs) regulate growth, reproduction, metabolic homeostasis, life span and stress resistance in worms, flies and mammals. A set of insulin producing cells (IPCs) in the Drosophila brain that express three ILPs (DILP2, 3 and 5) have been the main focus of interest in hormonal DILP signaling. Little is, however, known about factors that regulate DILP production and release by these IPCs. Here we show that the IPCs express the metabotropic GABA(B) receptor (GBR), but not the ionotropic GABA(A) receptor subunit RDL. Diminishing the GBR expression on these cells by targeted RNA interference abbreviates life span, decreases metabolic stress resistance and alters carbohydrate and lipid metabolism at stress, but not growth in Drosophila. A direct effect of diminishing GBR on IPCs is an increase in DILP immunofluorescence in these cells, an effect that is accentuated at starvation. Knockdown of irk3, possibly part of a G protein-activated inwardly rectifying K(+) channel that may link to GBRs, phenocopies GBR knockdown in starvation experiments. Our experiments suggest that the GBR is involved in inhibitory control of DILP production and release in adult flies at metabolic stress and that this receptor mediates a GABA signal from brain interneurons that may convey nutritional signals. This is the first demonstration of a neurotransmitter that inhibits insulin signaling in its regulation of metabolism, stress and life span in an invertebrate brain.

National Category
Biological Sciences
Research subject
Functional Zoomorphology
Identifiers
urn:nbn:se:su:diva-53298 (URN)10.1371/journal.pone.0015780 (DOI)000285793600039 ()21209905 (PubMedID)
Available from: 2011-01-21 Created: 2011-01-21 Last updated: 2017-12-11Bibliographically approved
2. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides
Open this publication in new window or tab >>Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides
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2010 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 7, e11480- p.Article in journal (Refereed) Published
Abstract [en]

In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a): Drosophila tachykinin (DTK), short neuropeptide F (sNPF) and ion transport peptide (ITP). These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-41306 (URN)10.1371/journal.pone.0011480 (DOI)000279637100010 ()
Available from: 2010-07-10 Created: 2010-07-10 Last updated: 2017-12-12Bibliographically approved

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