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Neuronal control of lipid metabolism by STR-2 G protein-coupled receptor promotes longevity in Caenorhabditis elegans

Dixit, A and Sandhu, A and Modi, S and Shashikanth, M and Koushika, SP and Watts, JL and Singh, V (2020) Neuronal control of lipid metabolism by STR-2 G protein-coupled receptor promotes longevity in Caenorhabditis elegans. In: Aging Cell, 19 (6).

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Official URL: https://doi.org/10.1111/acel.13160

Abstract

The G protein-coupled receptor (GPCR) encoding family of genes constitutes more than 6 of genes in Caenorhabditis elegans genome. GPCRs control behavior, innate immunity, chemotaxis, and food search behavior. Here, we show that C. elegans longevity is regulated by a chemosensory GPCR STR-2, expressed in AWC and ASI amphid sensory neurons. STR-2 function is required at temperatures of 20°C and higher on standard Escherichia coli OP50 diet. Under these conditions, this neuronal receptor also controls health span parameters and lipid droplet (LD) homeostasis in the intestine. We show that STR-2 regulates expression of delta-9 desaturases, fat-5, fat-6 and fat-7, and of diacylglycerol acyltransferase dgat-2. Rescue of the STR-2 function in either AWC and ASI, or ASI sensory neurons alone, restores expression of fat-5, dgat-2 and restores LD stores and longevity. Rescue of stored fat levels of GPCR mutant animals to wild-type levels, with low concentration of glucose, rescues its lifespan phenotype. In all, we show that neuronal STR-2 GPCR facilitates control of neutral lipid levels and longevity in C. elegans. © 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Item Type: Journal Article
Publication: Aging Cell
Publisher: Blackwell Publishing Ltd
Additional Information: This article belongs to Blackwell Publishing Ltd
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 05 Aug 2021 12:10
Last Modified: 05 Aug 2021 12:10
URI: http://eprints.iisc.ac.in/id/eprint/65655

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