Yeast Saccharomyces cerevisiae adiponectin receptor homolog Izh2 is involved in the regulation of zinc, phospholipid and pH homeostasisElectronic supplementary information (ESI) available. See DOI: 10.1039/c5mt00095e
The functional link between zinc homeostasis and membrane-related processes, including lipid metabolism regulation, extends from yeast to humans, and has a likely role in the pathogenesis of diabetes. The yeast Izh2 protein has been previously implicated in zinc ion homeostasis and in the regulation...
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| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
02-09-2015
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| Online Access: | Get full text |
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| Summary: | The functional link between zinc homeostasis and membrane-related processes, including lipid metabolism regulation, extends from yeast to humans, and has a likely role in the pathogenesis of diabetes. The yeast Izh2 protein has been previously implicated in zinc ion homeostasis and in the regulation of lipid and phosphate metabolism, but its precise molecular function is not known. We performed a chemogenomics experiment to determine the genes conferring resistance or sensitivity to different environmental zinc concentrations. We then determined at normal, depleted and excess zinc concentrations, the genetic interactions of
IZH2
at the genome-wide level and measured changes in the transcriptome caused by deletion of
IZH2
. We found evidence for an important cellular function of the Rim101 pathway in zinc homeostasis in neutral or acidic environments, and observed that phosphatidylinositol is a source of inositol when zinc availability is limited. Comparison of our experimental profiles with published gene expression and genetic interaction profiles revealed pleiotropic functions for Izh2. We propose that Izh2 acts as an integrator of intra- and extracellular signals in providing adequate cellular responses to maintain homeostasis under different external conditions, including - but not limited to - alterations in zinc concentrations.
Izh2 acts as an integrator of intra- and extracellular signals. It dispatches a single input signal - a change in extracellular Zn concentration - into regulatory networks of several cellular processes, whereby it acts as the second line of cellular adaptation to perturbations to zinc homeostasis. |
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| Bibliography: | 10.1039/c5mt00095e Electronic supplementary information (ESI) available. See DOI |
| ISSN: | 1756-5901 1756-591X |
| DOI: | 10.1039/c5mt00095e |