Zinc regulations

	An illuminating experience for zinc

Our understanding of how zinc is transported in and out of cells has become clearer thanks to work by chemists at Northwestern University, in Evanston, Illinois. The insight will improve our knowledge of disorders involving zinc metabolism.

Living cells require significant amounts of zinc for healthy function but little is known about how the metal is used or indeed how the cell controls its concentration so that damaging excesses do not build up.

Thomas O'Halloran and former graduate student Caryn Outten recently solved an important part of the puzzle. They have figured out how two sensor proteins control the pumps in the cell membrane that draw zinc in and out depending on the cell's needs. According to O'Halloran this is the first time a zinc regulatory protein has been accurately calibrated, "and it sets the stage for understanding the global mechanisms of

Thomas O'Halloran

cellular zinc trafficking," he says. Moreover, the team has demonstrated that there is no free-floating zinc within a cell, contrary to the received wisdom about this metal. Rather, all cellular zinc is bound up by proteins and cellular machinery that require this metal in order to function. The team suggests that there must also exist zinc "chaperone" proteins that escort the metal safely to the biochemical sites where it is needed once inside the cell. O'Halloran and geneticist Valeria Culotta of Johns Hopkins University discovered the first copper chaperone function in 1997.

The team used a bacterial model in Escherichia coli to study zinc regulation and observed that cells collect Zn(II)ions but once too much has accumulated in the cell it was quickly bound up in a protein, Zur. This binding process switches off the zinc intake pumps. If zinc continues to accumulate in the cell it may poison the cell. The next stage of the early warning system, combines zinc with the regulatory protein ZntR, which powers up the cellular zinc export pumps so that any unwanted zinc is quickly removed.

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The zinc regulatory system is so sensitive and finely tuned - at the femtomolar level - that the metal ions have no chance to float freely in the cell's cytoplasm before they are bound up in Zur or ZntR. "The zinc concentration is so low in between pump activity that free-floating zinc just doesn't exist," explains Outten, now working at Johns Hopkins Bloomberg School of Public Health. "It's a kinetic process - any zinc that shows up in the cell is immediately taken away, to work reactions in the cell, to bind to proteins such as Zur or ZntR or, if no zinc is needed, to be sent packing out of the cell."

Source: Sciencexpress ^*

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