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Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

Brankatschk M, Dunst S, Nemetschke L, Eaton S - Elife (2014)

Bottom Line: This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin.LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation.This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, Cell and Developmental Biology, Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.

ABSTRACT
The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

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In the last larval developmental stage DRNs enrich LTP.Panel shows numbers (see also Figure 2D) of DRNs (grey) and LTP positive DRNs (dark grey) from 1st, 2nd or early and mid 3rd instar (3rd−72h = 72hr and 3rd−96h = 96 hr after egg collection) larvae reared on yeast food.DOI:http://dx.doi.org/10.7554/eLife.02862.015
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fig2s2: In the last larval developmental stage DRNs enrich LTP.Panel shows numbers (see also Figure 2D) of DRNs (grey) and LTP positive DRNs (dark grey) from 1st, 2nd or early and mid 3rd instar (3rd−72h = 72hr and 3rd−96h = 96 hr after egg collection) larvae reared on yeast food.DOI:http://dx.doi.org/10.7554/eLife.02862.015

Mentions: To understand the CNS functions of LTP, we sought to identify the neurons where it accumulated. We first investigated whether LTP co-localized with Dilp2-positive neurons in early third instar larval brains. Dilp2 is present not only in IPCs, which lie dorso-lateral to the big commissure, but also on three neurons per hemisphere that do not produce Dilps. These neurons recruit Dilp2 from IPCs using IMPL2, a Dilp2-binding protein (Bader et al., 2013). Although each hemisphere contains 7-8 neurons that express IMPL2 at this stage, only 3 of these detectably recruit Dilp2, and 2 of these 3 also accumulate LTP. These neurons can be unambiguously identified by the presence of both LTP and Dilp2, by their position, by lack of expression of dilp2-GAL4, and by expression of impL2-GAL4 (Figure 2, Figure 2—figure supplement 1). Henceforth, we refer to these neurons as Dilp2-recruiting neurons (DRNs). Starting in the third larval instar, LTP accumulates on two specific DRNs located dorsal to the big commissure (Figure 2A,C,D, Figure 2—figure supplement 2). Although LTP is found on other neurons at earlier stages, its accumulation on DRNs is developmentally regulated. We also sometimes (6/20 sampled CNS) detect LTP on a subset of IPC neurons (Figure 2B). Thus, upon entering the brain, LTP accumulates on IPCs and specific neurons that recruit Dilp2.10.7554/eLife.02862.013Figure 2.LTP accumulates on neurons positive for Dilp2 and IMPL2.


Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

Brankatschk M, Dunst S, Nemetschke L, Eaton S - Elife (2014)

In the last larval developmental stage DRNs enrich LTP.Panel shows numbers (see also Figure 2D) of DRNs (grey) and LTP positive DRNs (dark grey) from 1st, 2nd or early and mid 3rd instar (3rd−72h = 72hr and 3rd−96h = 96 hr after egg collection) larvae reared on yeast food.DOI:http://dx.doi.org/10.7554/eLife.02862.015
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4210815&req=5

fig2s2: In the last larval developmental stage DRNs enrich LTP.Panel shows numbers (see also Figure 2D) of DRNs (grey) and LTP positive DRNs (dark grey) from 1st, 2nd or early and mid 3rd instar (3rd−72h = 72hr and 3rd−96h = 96 hr after egg collection) larvae reared on yeast food.DOI:http://dx.doi.org/10.7554/eLife.02862.015
Mentions: To understand the CNS functions of LTP, we sought to identify the neurons where it accumulated. We first investigated whether LTP co-localized with Dilp2-positive neurons in early third instar larval brains. Dilp2 is present not only in IPCs, which lie dorso-lateral to the big commissure, but also on three neurons per hemisphere that do not produce Dilps. These neurons recruit Dilp2 from IPCs using IMPL2, a Dilp2-binding protein (Bader et al., 2013). Although each hemisphere contains 7-8 neurons that express IMPL2 at this stage, only 3 of these detectably recruit Dilp2, and 2 of these 3 also accumulate LTP. These neurons can be unambiguously identified by the presence of both LTP and Dilp2, by their position, by lack of expression of dilp2-GAL4, and by expression of impL2-GAL4 (Figure 2, Figure 2—figure supplement 1). Henceforth, we refer to these neurons as Dilp2-recruiting neurons (DRNs). Starting in the third larval instar, LTP accumulates on two specific DRNs located dorsal to the big commissure (Figure 2A,C,D, Figure 2—figure supplement 2). Although LTP is found on other neurons at earlier stages, its accumulation on DRNs is developmentally regulated. We also sometimes (6/20 sampled CNS) detect LTP on a subset of IPC neurons (Figure 2B). Thus, upon entering the brain, LTP accumulates on IPCs and specific neurons that recruit Dilp2.10.7554/eLife.02862.013Figure 2.LTP accumulates on neurons positive for Dilp2 and IMPL2.

Bottom Line: This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin.LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation.This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular, Cell and Developmental Biology, Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.

ABSTRACT
The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

Show MeSH