By: Marc Pilon, Department of Chemistry and Molecular Biology, University of Gothenburg

Title: The PAQR-2/IGLR-2 Complex is Essential for Membrane Homeostasis in C. elegans.

Abstract

Surprisingly very little is known about the mechanisms responsible for membrane homeostasis in eukaryotes. Using C. elegans, we have discovered the first sensor/regulator of membrane homeostasis in animals: it is composed of two proteins, PAQR-2 and IGLR-2, which are homologs of the mammalian adiponectin receptors and of LRIG-type proteins, respectively. This protein complex is essential for C. elegans to regulate membrane composition when challenged by low temperature or by diets rich in saturated fatty acids, which can be derived from glucose. Mosaic analysis reveals that IGLR-2 and PAQR-2 acts cell non-autonomously in hypodermal and gonad sheath cells to regulate membrane homeostasis systemically. Using FRAP (Fluorescence Recovery After Photobleaching) on living worms, we found that cultivation in the presence of glucose causes a lethal 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. Importantly, 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; PAQR-2 and IGLR-2 therefore represent an entirely new pathway essential for survival in the presence of glucose. Using bimolecular fluorescence complementation (BiFC), 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.