The yeast Saccharomyces cerevisiae contains a family of zinc responsive membrane proteins named IZH1-4 (Implicated in Zinc Homeostasis), which belong to a superfamily of proteins known as the PAQRs (Progestin AdipoQ Receptor). These putative membrane proteins contain at least seven transmembrane domains. The PAQR family of proteins consists of known osmotin, adiponectin and progesterone receptors that are distantly related to alkaline ceramidases. The objective of this study is to characterize the role of the PAQR family in lipid mediating signaling. We have evidence that the PAQR family, when overexpressed or in the presence of their specific ligand, represses ZRT1, a high affinity zinc transporter gene, and FET3, a high affinity iron transporter gene, suggesting a role for these proteins in zinc- and iron-uptake. The repression of these genes requires a sphingoid-base dependent signal transduction pathway involving Ras-cAMP/PKA and the Snf1p AMP-dependent kinase. This pathway ultimately governs a competition between the Nrg1p/Nrg2p and Msn2p/Msn4p transcription factors for binding sites in the promoter region of ZRT1 and FET3.

We also found that human AdipoR1 represses FET3 with the addition of adiponectin. Furthermore, the addition of TNF-α partially alleviates repression by AdipoR1. However, when adiponectin and TNF-α were added together, FET3 repression was not alleviated. Finally, we examined labeled-adiponectin and TNF-α binding to cells overexpresing AdipoR1. Bound TNF-α levels fell when unlabeled adiponectin was added; however, the addition of unlabeled TNF-α displaced labeled-adiponectin. Thus, adiponectin and TNF-α compete for binding to yeast cells expressing AdipoR1.