RRC ID 28903
Author Subramanian M, Jayakumar S, Richhariya S, Hasan G.
Title Loss of IP3 receptor function in neuropeptide secreting neurons leads to obesity in adult Drosophila.
Journal BMC Neurosci
Abstract BACKGROUND:Intracellular calcium signaling regulates a variety of cellular and physiological processes. The inositol 1,4,5 trisphosphate receptor (IP3R) 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 IP3R (itprku) 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 IP3R, 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 itprku 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.
Volume 14
Pages 157
Published 2013-12-18
DOI 10.1186/1471-2202-14-157
PII 1471-2202-14-157
PMID 24350669
PMC PMC3878400
MeSH Animals Calcium Signaling / physiology Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Gene Knockdown Techniques Immunohistochemistry Inositol 1,4,5-Trisphosphate Receptors / genetics Inositol 1,4,5-Trisphosphate Receptors / metabolism* Lipid Metabolism Neurons / metabolism* Neuropeptides / metabolism Obesity / genetics Obesity / metabolism* Real-Time Polymerase Chain Reaction
IF 2.811
Times Cited 13
WOS Category NEUROSCIENCES
Resource
Drosophila 1063R-2