Achievement

Zinc, the second most abundant element in the brain, interacts with tissue plasminogen activator (tPA), and that interaction results in the neutralization of both zinc's and tPA's neurotoxicity, and moreover we reported that zinc is sequestered into neuronal cells. Trainee Jaime Emmetsberger in Dr. Tsirka's lab and past trainee Martine Mirrione continued the work to determine the molecular players that mediate zinc sequestration. They identified the specific domain where tPA physically interacts with the zinc transporter ZIP4. The interaction brings zinc into the neurons, modifies the actin cytoskeleton of the cells and places into lysosomes. They also defined the localization of the zinc transporter in specific neurons of the mouse brain tissue. The molecular signalizng pathway that is involved in the interactions between tPA, zinc transporter and neuronal zinc sequestration were defined. This work is now in press in the Journal of Neuroscience.