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Loss of IP(3) receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila
BACKGROUND: Intracellular calcium signaling regulates a variety of cellular and physiological processes. The inositol 1,4,5 trisphosphate receptor (IP(3)R) is a ligand gated calcium channel present on the membranes of endoplasmic reticular stores. In previous work we have shown that Drosophila mutan...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878400/ https://www.ncbi.nlm.nih.gov/pubmed/24350669 http://dx.doi.org/10.1186/1471-2202-14-157 |
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author | Subramanian, Manivannan Jayakumar, Siddharth Richhariya, Shlesha Hasan, Gaiti |
author_facet | Subramanian, Manivannan Jayakumar, Siddharth Richhariya, Shlesha Hasan, Gaiti |
author_sort | Subramanian, Manivannan |
collection | PubMed |
description | BACKGROUND: Intracellular calcium signaling regulates a variety of cellular and physiological processes. The inositol 1,4,5 trisphosphate receptor (IP(3)R) is a ligand gated calcium channel present on the membranes of endoplasmic reticular stores. In previous work we have shown that Drosophila mutants for the IP(3)R (itpr( ku )) become unnaturally obese as adults with excessive storage of lipids on a normal diet. While the phenotype manifests in cells of the fat body, genetic studies suggest dysregulation of a neurohormonal axis. RESULTS: We show that knockdown of the IP(3)R, either in all neurons or in peptidergic neurons alone, mimics known itpr mutant phenotypes. The peptidergic neuron domain includes, but is not restricted to, the medial neurosecretory cells as well as the stomatogastric nervous system. Conversely, expression of an itpr( + ) cDNA in the same set of peptidergic neurons rescues metabolic defects of itpr( ku ) mutants. Transcript levels of a gene encoding a gastric lipase CG5932 (magro), which is known to regulate triacylglyceride storage, can be regulated by itpr knockdown and over-expression in peptidergic neurons. Thus, the focus of observed itpr mutant phenotypes of starvation resistance, increased body weight, elevated lipid storage and hyperphagia derive primarily from peptidergic neurons. CONCLUSIONS: The present study shows that itpr function in peptidergic neurons is not only necessary but also sufficient for maintaining normal lipid metabolism in Drosophila. Our results suggest that intracellular calcium signaling in peptidergic neurons affects lipid metabolism by both cell autonomous and non-autonomous mechanisms. |
format | Online Article Text |
id | pubmed-3878400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38784002014-01-03 Loss of IP(3) receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila Subramanian, Manivannan Jayakumar, Siddharth Richhariya, Shlesha Hasan, Gaiti BMC Neurosci Research Article BACKGROUND: Intracellular calcium signaling regulates a variety of cellular and physiological processes. The inositol 1,4,5 trisphosphate receptor (IP(3)R) is a ligand gated calcium channel present on the membranes of endoplasmic reticular stores. In previous work we have shown that Drosophila mutants for the IP(3)R (itpr( ku )) become unnaturally obese as adults with excessive storage of lipids on a normal diet. While the phenotype manifests in cells of the fat body, genetic studies suggest dysregulation of a neurohormonal axis. RESULTS: We show that knockdown of the IP(3)R, either in all neurons or in peptidergic neurons alone, mimics known itpr mutant phenotypes. The peptidergic neuron domain includes, but is not restricted to, the medial neurosecretory cells as well as the stomatogastric nervous system. Conversely, expression of an itpr( + ) cDNA in the same set of peptidergic neurons rescues metabolic defects of itpr( ku ) mutants. Transcript levels of a gene encoding a gastric lipase CG5932 (magro), which is known to regulate triacylglyceride storage, can be regulated by itpr knockdown and over-expression in peptidergic neurons. Thus, the focus of observed itpr mutant phenotypes of starvation resistance, increased body weight, elevated lipid storage and hyperphagia derive primarily from peptidergic neurons. CONCLUSIONS: The present study shows that itpr function in peptidergic neurons is not only necessary but also sufficient for maintaining normal lipid metabolism in Drosophila. Our results suggest that intracellular calcium signaling in peptidergic neurons affects lipid metabolism by both cell autonomous and non-autonomous mechanisms. BioMed Central 2013-12-18 /pmc/articles/PMC3878400/ /pubmed/24350669 http://dx.doi.org/10.1186/1471-2202-14-157 Text en Copyright © 2013 Subramanian et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Subramanian, Manivannan Jayakumar, Siddharth Richhariya, Shlesha Hasan, Gaiti Loss of IP(3) receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila |
title | Loss of IP(3) receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila |
title_full | Loss of IP(3) receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila |
title_fullStr | Loss of IP(3) receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila |
title_full_unstemmed | Loss of IP(3) receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila |
title_short | Loss of IP(3) receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila |
title_sort | loss of ip(3) receptor function in neuropeptide secreting neurons leads to obesity in adult drosophila |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878400/ https://www.ncbi.nlm.nih.gov/pubmed/24350669 http://dx.doi.org/10.1186/1471-2202-14-157 |
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