Caenorhabditis Elegans PAQR-2 and IGLR-2 Protect Against Glucose Toxicity by Modulating Membrane Lipid Composition

Overview

Journal PLoS Genet

Specialty Genetics

Date 2016 Apr 16

PMID 27082444

Citations 37

Authors

Emma Svensk

Ranjan Devkota

Marcus Stahlman

Parmida Ranji

Manish Rauthan

Fredrik Magnusson

Sofia Hammarsten

Maja Johansson

Jan Boren

Marc Pilon

Affiliations

Soon will be listed here.

Abstract

In spite of the worldwide impact of diabetes on human health, the mechanisms behind glucose toxicity remain elusive. Here we show that C. elegans mutants lacking paqr-2, the worm homolog of the adiponectin receptors AdipoR1/2, or its newly identified functional partner iglr-2, are glucose intolerant and die in the presence of as little as 20 mM glucose. Using FRAP (Fluorescence Recovery After Photobleaching) on living worms, we found that cultivation in the presence of glucose causes a decrease in membrane fluidity in paqr-2 and iglr-2 mutants and that genetic suppressors of this sensitivity act to restore membrane fluidity by promoting fatty acid desaturation. The essential roles of paqr-2 and iglr-2 in the presence of glucose are completely independent from daf-2 and daf-16, the C. elegans homologs of the insulin receptor and its downstream target FoxO, respectively. Using bimolecular fluorescence complementation, we also show that PAQR-2 and IGLR-2 interact on plasma membranes and thus may act together as a fluidity sensor that controls membrane lipid composition.

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