Zinc is an essential element, and alterations in systemic zinc homeostasis have been linked to diseases such as adolescent nutritional dwarfism, acrodermatitis enteropathica and repression of the immune system. A greater understanding of zinc homeostasis at the cellular and molecular level is essential to human health in that it will directly impact the ability to diagnose and treat zinc related diseases by providing markers by which to assess zinc status and therapeutic targets. Two central questions are addressed in this proposal. Is zinc stored within cells in a bio- available form, and if so, which proteins are involved in zinc transit through these compartments? The research described in the proposal will combine fluorescent microscopy studies with biophysical and proteomic approaches to identify zinc rich cellular compartments and isolate the proteins associated with these vesicles. These studies will resolve several competing hypotheses regarding zinc homeostasis and can potentially reveal a completely novel pathway for trafficking and utilization of this element.
| Brown, Nina M; Torres, Andrew S; Doan, Peter E et al. (2004) Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase. Proc Natl Acad Sci U S A 101:5518-23 |
