The IGFBP7 homolog Imp-L2 promotes insulin signaling in distinct neurons of the <i>Drosophila</i> brain

Bader, R.; Sarraf-Zadeh, Ladan; Peters, Marc; Moderau, Nina; Stocker, Hugo; Köhler, Katja; Pankratz, Michael J.; Hafen, Ernst

doi:10.1242/jcs.120261

Cited by 62 publications

(58 citation statements)

References 27 publications

(33 reference statements)

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“…The neuroanatomy of the hugin neurons, especially exemplified by the projection pattern that connects the SOG to the protocerebrum, suggests that the SOG/protocerebrum corridor encompassing the hugin neuronal projections may play an important role in action selection of motor programs underlying feeding and locomotion (Figure 9B). The hugin projections to the protocerebrum and the connections to the gustatory cells and the insulin-producing cells [49],[78], would process external and internal sensory cues, and determine which motor programs modulating feeding and locomotion are selected.…”

Section: Discussionmentioning

confidence: 99%

Selection of Motor Programs for Suppressing Food Intake and Inducing Locomotion in the Drosophila Brain

Schoofs

Hückesfeld²,

Schlegel³

et al. 2014

PLoS Biol

112

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Section: Discussionmentioning

confidence: 99%

Selection of Motor Programs for Suppressing Food Intake and Inducing Locomotion in the Drosophila Brain

Schoofs

Hückesfeld²,

Schlegel³

et al. 2014

PLoS Biol

112

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“…ILP2 is also released within the brain (Bader et al 2013). By following IPCs during larval development, we observed that IPC axons and dendrites extend over greater distances until the early third instar larval stage.…”

Section: Discussionmentioning

confidence: 99%

Insight into Insulin Secretion from Transcriptome and Genetic Analysis of Insulin-Producing Cells of Drosophila

Cao

et al. 2014

Genetics

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Insulin-producing cells (IPCs) in the Drosophila brain produce and release insulin-like peptides (ILPs) to the hemolymph. ILPs are crucial for growth and regulation of metabolic activity in flies, functions analogous to those of mammalian insulin and insulin-like growth factors (IGFs). To identify components functioning in IPCs to control ILP production, we employed genomic and candidate gene approaches. We used laser microdissection and messenger RNA sequencing to characterize the transcriptome of larval IPCs. IPCs highly express many genes homologous to genes active in insulin-producing β-cells of the mammalian pancreas. The genes in common encode ILPs and proteins that control insulin metabolism, storage, secretion, β-cell proliferation, and some not previously linked to insulin production or β-cell function. Among these novelties is unc-104, a kinesin 3 family gene, which is more highly expressed in IPCs compared to most other neurons. Knockdown of unc-104 in IPCs impaired ILP secretion and reduced peripheral insulin signaling. Unc-104 appears to transport ILPs along axons. As a complementary approach, we tested dominant-negative Rab genes to find Rab proteins required in IPCs for ILP production or secretion. Rab1 was identified as crucial for ILP trafficking in IPCs. Inhibition of Rab1 in IPCs increased circulating sugar levels, delayed development, and lowered weight and body size. Immunofluorescence labeling of Rab1 showed its tight association with ILP2 in the Golgi of IPCs. Unc-104 and Rab1 join other proteins required for ILP transport in IPCs.

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“…Brains were fixed in 4% paraformaldehyde for 30 min, rinsed, blocked in 5% normal goat serum, and incubated overnight at 4°C with primaries: goat anti-GFP-FITC (abcam, ab26662), 1:500; rabbit anti-DH44 (Cabrero et al, 2002) (gift of Jan Veenstra), 1:1000; guinea pig anti-Dilp2 (Bader et al, 2013) (Pankratz lab), 1:500 and rabbit anti-DMS (Schoofs et al, 1993; Park et al, 2008) (gift of Luc van den Bosch and Liliane Schoofs), 1:500. Tissues were rinsed and incubated overnight at 4°C in secondaries: anti-rabbit Alexa Fluor 633 (Invitrogen, A-21070) and anti-guinea pig Alexa Fluor 568 (Invitrogen, A-11075), both 1:500.…”

Section: Methodsmentioning

confidence: 99%

Synaptic transmission parallels neuromodulation in a central food-intake circuit

Schlegel

Texada

Miroschnikow

et al. 2016

eLife

134

158

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NeuromedinU is a potent regulator of food intake and activity in mammals. In Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in the Drosophila larval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.DOI: http://dx.doi.org/10.7554/eLife.16799.001

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The IGFBP7 homolog Imp-L2 promotes insulin signaling in distinct neurons of the Drosophila brain

Cited by 62 publications

References 27 publications

Selection of Motor Programs for Suppressing Food Intake and Inducing Locomotion in the Drosophila Brain

Selection of Motor Programs for Suppressing Food Intake and Inducing Locomotion in the Drosophila Brain

Insight into Insulin Secretion from Transcriptome and Genetic Analysis of Insulin-Producing Cells of Drosophila

Synaptic transmission parallels neuromodulation in a central food-intake circuit

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