Zinc is essential for brain function but its handling by the cells of the nervous system, neurons, is not well understood. In our collaborative project we aimed to understand how neurons respond to changes in zinc and how they handle this ion using multiple transporters that have been associated with zinc in cells. We have shown that sound processing in the brain changes the expression of a major zinc transporter, ZnT1, a protein found on the neuronal membrane that drives zinc out of the neurons. We further showed that ZnT1 interacts with an important modulator of neuronal responses, and thereby can affect the neuronal responses. To understand how the ZnT1 transporter can drive the zinc out of the neurons we used fluorescence imaging microscopy and identified a novel mechanism of exchange between zinc and calcium, which is found at a large gradient across the neuronal membrane. Finally, we identified two more zinc transporters that are essential for zinc physiology, we show that ZIP1 and ZIP3 proteins are responsible for uptake of zinc into the neurons, but in distinct locations of the neuronal circuits. We have shown that this zinc uptake is important for normal neuronal function and that when ZIP3 is not present in the neurons, they are rescued from toxicity and degeneration. Altogether, our studies describe the important molecular targets of zinc in the brain and how regulation of zinc signals affects neuronal behavior and survival.
|Effective start/end date||1/01/16 → …|
- United States-Israel Binational Science Foundation (BSF)