RESUMEN
The properties of cellular membranes are critical for most cellular functions and are influenced by several parameters including phospholipid composition, integral and peripheral membrane proteins, and environmental conditions such as temperature. We previously showed that the C. elegans paqr-2 and iglr-2 mutants have a defect in membrane homeostasis and exhibit several distinct phenotypes, including a characteristic tail tip defect and cold intolerance. In the present study we report that screening for novel mutants with these 2 defects can lead to the identification of genes that are important contributors to membrane properties. In particular we isolated 3 novel alleles of sma-1, the C. elegans homolog of ßH spectrin, and 2 novel alleles of dpy-23, which encodes the C. elegans homolog of the AP2 µ subunit. We also show that sma-1 and dpy-23 act on membrane properties in pathways distinct from that of paqr-2 and iglr-2.
RESUMEN
[This corrects the article DOI: 10.1371/journal.pgen.1005982.].
RESUMEN
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.