Caenorhabditis elegans PAQR-2 and IGLR-2 Protect against Glucose Toxicity by Modulating Membrane Lipid Composition

被引：60

作者：

Svensk, Emma ^{[1
]}

Devkota, Ranjan ^{[1
]}

Stahlman, Marcus ^{[2
]}

Ranji, Parmida ^{[1
]}

Rauthan, Manish ^{[1
]}

Magnusson, Fredrik ^{[1
]}

Hammarsten, Sofia ^{[1
]}

Johansson, Maja ^{[1
]}

Boren, Jan ^{[2
]}

Pilon, Marc ^{[1
]}

机构：

[1] Univ Gothenburg, Dept Chem & Mol Biol, Gothenburg, Sweden

[2] Univ Gothenburg, Inst Med, Wallenberg Lab, Dept Mol & Clin Med, Gothenburg, Sweden

来源：

PLOS GENETICS | 2016年 / 12卷 / 04期

基金：

美国国家卫生研究院;

关键词：

FATTY-ACIDS; C-ELEGANS; LIFE-SPAN; ADIPONECTIN RECEPTOR; BIOLOGICAL-MEMBRANES; GROWTH-FACTOR; METABOLISM; MECHANISMS; ADAPTATION; FLUIDITY;

D O I：

10.1371/journal.pgen.1005982

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 20mM 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.

引用

页数：24

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