| Zinc is an essential trace element, and organisms are sensitive to both zinc deficiency and zinc excess. In both prokaryotes and eukaryotes, zinc metabolism and homeostasis are known to involve zinc transporters and zinc-sensing transcription factors. Zinc chaperones have been hypothesized but not yet identified. While all organisms appear to utilize complex mechanisms to regulate zinc metabolism and homeostasis, multicellular organisms require the coordinated expression and regulation of a series of proteins to absorb, distribute, store, and excrete zinc throughout the entirety of the animal. These mechanisms are not well defined. Caenorhabditis elegans is a multicellular organism that has relatively simple anatomy and is ideal for molecular and genetic analysis. The development of C. elegans as a model system to study zinc metabolism will fill an important need since yeast lack the complexities of a multicellular animal and the genetic analysis of rodents is challenging.;Two approaches were utilized to elucidate novel mechanisms regulating zinc metabolism in C. elegans: (1). An analysis of genes predicted to be involved in zinc metabolism. Cation diffusion facilitator (CDF) proteins are transporters that lower cytosolic zinc by moving zinc across the plasma membrane or into organelles. C. elegans has 14 genes that encode predicted CDF proteins, and three loss-of-function mutations were studied. CDF-1 and SUR-7 function to promote normal development at low dietary zinc and protect the animal from high dietary zinc. CDF-2 functions to promote robust population growth and zinc storage. The analyses indicate that cdf-1, cdf-2, and sur-7 independently function to regulate zinc metabolism and that CDF-1 and CDF-2 compete for intestinal cell zinc. (2). A forward genetic screen identified nineteen mutations that cause resistance to high dietary zinc. The nineteen mutations affect three or more independent genes, and cloning is on-going. Collectively, these studies have defined the functions of three CDF proteins, identified novel genes involved in zinc metabolism, and demonstrated the utility of using C. elegans as a model for studying zinc metabolism. |
