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

Svensk, Emma; Devkota, Ranjan; Ståhlman, Marcus; Ranji, Parmida; Rauthan, Manish; Magnusson, Fredrik; Hammarsten, Sofia; Johansson, Monika; Borén, Jan; Pilon, Marc

doi:10.1371/journal.pgen.1005982

Cited by 66 publications

(139 citation statements)

References 82 publications

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“…The worms were cultured on normal growing media plates (NGM plates) and the E. coli strain OP50 was used as a food source. The worms were maintained at the optimal temperature of 25 ° C (Sulston et al, 1988; Svensk et al, 2016). Wild type cells of S. cerevisiae (S228C background) were cultured and maintained in YPD media (Hill et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

Nuclear envelope budding is a response to cellular stress

Panagaki

Croft

Keuenhof

et al. 2018

Preprint

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Eukaryotic cells are defined by the compartmentalization of the cytoplasm into organelles, the largest of which is the nucleus, which contains the cellular DNA. Transport into and out of the nucleus is highly regulated and is traditionally thought to occur solely through nuclear pores. However, a small number of papers has repeatedly shown vesicular budding from the nuclear envelopes in different organisms. We used electron microscopy to identify such nuclear envelope budding events in a human cell line, Caenorhabditis elegans worms, the two yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe and the parasitic protist Trypanosoma brucei. Progressing to electron tomography, the finer details of the 3D architecture of such budding events was revealed. We summarize all the organisms in which this mode of translocation over the nuclear envelope has been observed and conclude that this may be a fundamental, evolutionary conserved mechanism of transport inside eukaryotic cells.

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Section: Methodsmentioning

confidence: 99%

Nuclear envelope budding is a response to cellular stress

Panagaki

Croft

Keuenhof

et al. 2018

Preprint

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“…We quantify it by measuring the diffusion coefficient of membrane lipids, which is inversely proportional to membrane viscosity. The acyl chain composition of membrane lipids is an important determinant of membrane fluidity and is tightly controlled in bacteria [5][6][7] , fungi 8,9 , worms 10,11 , flies 12 , and vertebrates 13,14 . Saturated lipid acyl chains tend to form non-fluid, tightly packed gel phases at physiological temperatures, whereas unsaturated lipid acyl chains fluidize the bilayer.…”

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confidence: 99%

Regulation of lipid saturation without sensing membrane fluidity

et al. 2020

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Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. We have reconstituted the core machinery for regulating lipid saturation in baker's yeast to study its molecular mechanism. By combining molecular dynamics simulations with experiments, we uncover a remarkable sensitivity of the transcriptional regulator Mga2 to the abundance, position, and configuration of double bonds in lipid acyl chains, and provide insights into the molecular rules of membrane adaptation. Our data challenge the prevailing hypothesis that membrane fluidity serves as the measured variable for regulating lipid saturation. Rather, we show that Mga2 senses the molecular lipid-packing density in a defined region of the membrane. Our findings suggest that membrane property sensors have evolved remarkable sensitivities to highly specific aspects of membrane structure and dynamics, thus paving the way toward the development of genetically encoded reporters for such properties in the future.

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“…2A). We found that the interaction between PAQR-2 and IGLR-2 in the gonad sheath cell membrane, where they are most abundantly expressed (9), was highly dynamic and that the strength of their interaction correlated with membrane rigidity across a range of conditions ( Fig. 2B-E).…”

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confidence: 85%

AdipoR2 is Essential for Membrane Lipid Homeostasis in Response to Dietary Saturated Fats

Devkota

Ruiz

Palmgren

et al. 2020

Preprint

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Membrane lipid composition influences vital processes in all types of cells. The mechanisms by which cells maintain membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remain largely unknown. In an attempt to discover such mechanisms, we performed an unbiased forward genetic screen in Caenorhabditis elegans and conclude that the adiponectin receptor 2 (AdipoR2) pathway is essential to prevent saturated fat-mediated cellular toxicity. Transcriptomics, lipidomics and membrane property analyses in human HEK293 cells and primary human endothelial cells further support our conclusion that the essential function of AdipoR2 is to respond to membrane rigidification by promoting fatty acid desaturation. Our results demonstrate that AdipoR2-dependent regulation of membrane homeostasis is a fundamental mechanism conserved from nematodes to mammals that prevents saturated fat-mediated lipotoxicity.ONE SENTENCE SUMMARYThe AdipoR2 protein insures membrane homeostasis in response to dietary saturated fatty acids that promote membrane rigidification.

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

Cited by 66 publications

References 82 publications

Nuclear envelope budding is a response to cellular stress

Nuclear envelope budding is a response to cellular stress

Regulation of lipid saturation without sensing membrane fluidity

AdipoR2 is Essential for Membrane Lipid Homeostasis in Response to Dietary Saturated Fats

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