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Insulin production and signaling in renal tubules of Drosophila is under control of tachykinin-related peptide and regulates stress resistance.

Söderberg JA, Birse RT, Nässel DR - PLoS ONE (2011)

Bottom Line: Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype.Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation.Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Stockholm University, Stockholm, Sweden.

ABSTRACT
The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

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Manipulations of DILP5 expression in larval tubules also affect lifespan during stress.Over expression or knockdown of DILP5 in principal cells of feeding third instar larvae also affects survival at metabolic stress. Larvae were kept without food on a wet filter paper. Experiments run in triplicate. Knockdown by C324/Dilp5-RNAi increased median lifespan by almost 25% (P<0.01 to both controls; Log rank test; n = 30 for the different genotypes) and over expression by C324/UAS-Dilp5 decreased lifespan by the same amount (P<0.001 to both controls; n = 30 for the different genotypes).
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pone-0019866-g009: Manipulations of DILP5 expression in larval tubules also affect lifespan during stress.Over expression or knockdown of DILP5 in principal cells of feeding third instar larvae also affects survival at metabolic stress. Larvae were kept without food on a wet filter paper. Experiments run in triplicate. Knockdown by C324/Dilp5-RNAi increased median lifespan by almost 25% (P<0.01 to both controls; Log rank test; n = 30 for the different genotypes) and over expression by C324/UAS-Dilp5 decreased lifespan by the same amount (P<0.001 to both controls; n = 30 for the different genotypes).

Mentions: Finally, since Dilp5 RNA and peptide are enriched also in larval renal tubules (Fig. 1F, L) (see also FlyAtlas; [34]), we investigated whether local insulin signaling contributes to lifespan regulation in larvae. We used the C324 driver to diminish or over-express Dilp5 in the renal tubules of feeding third instar larvae (Fig. 9). Control larvae that were kept on a wet filter paper and no access to food displayed a median lifespan of about 6.5 h. With increased DILP5 they displayed a reduction by 1.5 h (p<0.001) whereas with diminished DILP5 lifespan increased by the same time (p<0.01). This suggests that also in the feeding larvae DILP5 signaling in the renal tubules plays a role in metabolic stress responses.


Insulin production and signaling in renal tubules of Drosophila is under control of tachykinin-related peptide and regulates stress resistance.

Söderberg JA, Birse RT, Nässel DR - PLoS ONE (2011)

Manipulations of DILP5 expression in larval tubules also affect lifespan during stress.Over expression or knockdown of DILP5 in principal cells of feeding third instar larvae also affects survival at metabolic stress. Larvae were kept without food on a wet filter paper. Experiments run in triplicate. Knockdown by C324/Dilp5-RNAi increased median lifespan by almost 25% (P<0.01 to both controls; Log rank test; n = 30 for the different genotypes) and over expression by C324/UAS-Dilp5 decreased lifespan by the same amount (P<0.001 to both controls; n = 30 for the different genotypes).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3091884&req=5

pone-0019866-g009: Manipulations of DILP5 expression in larval tubules also affect lifespan during stress.Over expression or knockdown of DILP5 in principal cells of feeding third instar larvae also affects survival at metabolic stress. Larvae were kept without food on a wet filter paper. Experiments run in triplicate. Knockdown by C324/Dilp5-RNAi increased median lifespan by almost 25% (P<0.01 to both controls; Log rank test; n = 30 for the different genotypes) and over expression by C324/UAS-Dilp5 decreased lifespan by the same amount (P<0.001 to both controls; n = 30 for the different genotypes).
Mentions: Finally, since Dilp5 RNA and peptide are enriched also in larval renal tubules (Fig. 1F, L) (see also FlyAtlas; [34]), we investigated whether local insulin signaling contributes to lifespan regulation in larvae. We used the C324 driver to diminish or over-express Dilp5 in the renal tubules of feeding third instar larvae (Fig. 9). Control larvae that were kept on a wet filter paper and no access to food displayed a median lifespan of about 6.5 h. With increased DILP5 they displayed a reduction by 1.5 h (p<0.001) whereas with diminished DILP5 lifespan increased by the same time (p<0.01). This suggests that also in the feeding larvae DILP5 signaling in the renal tubules plays a role in metabolic stress responses.

Bottom Line: Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype.Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation.Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, Stockholm University, Stockholm, Sweden.

ABSTRACT
The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.

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