title: Caenorhabditis elegans PAQR-2 and IGLR-2 Protect against Glucose Toxicity by Modulating Membrane Lipid Composition.
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.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Svensk
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Devkota
authors.affiliation: Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ståhlman
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Parmida
authors.initials: P
authors.lastname: Ranji
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Manish
authors.initials: M
authors.lastname: Rauthan
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Magnusson
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Hammarsten
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Maja
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Marc
authors.initials: M
authors.lastname: Pilon
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D051858:Forkhead Transcription Factors / Q000235:genetics; D005947:Glucose / Q000633:toxicity*; D008560:Membrane Fluidity / Q000235:genetics* / Q000502:physiology; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C000609792:IGLR-2 protein, C elegans; D008563:Membrane Lipids; D008565:Membrane Proteins; C587163:PAQR-2 protein, C elegans; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D005947:Glucose