1. The C. elegans PAQR-2 and IGLR-2 membrane homeostasis proteins are uniquely essential for tolerating dietary saturated fats.
- Author
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Devkota, Ranjan, Henricsson, Marcus, Borén, Jan, and Pilon, Marc
- Subjects
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CAENORHABDITIS elegans , *MEMBRANE proteins , *FLUORESCENCE resonance energy transfer , *SATURATED fatty acids , *FAT , *ADIPONECTIN , *FAT content of food - Abstract
How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we report the first whole-organism (Caenorhabditis elegans) forward genetic screen to identify genes essential for tolerance to dietary saturated fatty acids (SFAs). We found that only the PAQR-2/IGLR-2 pathway, homologous to the human adiponectin receptor 2 (AdipoR2) pathway, is uniquely essential to prevent SFA-mediated toxicity. When provided a SFA-rich diet, worms lacking either protein accumulate an excess of SFAs in their membrane phospholipids, which is accompanied by membrane rigidification. Additionally, we used fluorescence resonance energy transfer (FRET) to show that the interaction between PAQR-2 and IGLR-2 is regulated by membrane fluidity, suggesting a mechanism by which this protein complex senses membrane properties. We also created versions of PAQR-2 that lacked parts of the cytoplasmic N-terminal domain and showed that these were still functional, though still dependent on the interaction with IGLR-2. We conclude that membrane homeostasis via the PAQR-2/IGLR-2 fluidity sensor is the only pathway specifically essential for the non-toxic uptake of dietary SFAs in C. elegans. Unlabelled Image • We screened for genes essential to tolerate dietary saturated fats in C. elegans. • The screen identified novel alleles of only two genes: paqr-2 and iglr-2. • PAQR-2 and ILGLR-2 are membrane proteins important for membrane homeostasis. • The interaction between PAQR-2 and IGLR-2 is induced by membrane rigidification. • The cytoplasmic domain of PAQR-2 is not essential for its function. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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