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Molecular Medicine

, Volume 13, Issue 7–8, pp 337–343 | Cite as

Mechanism and Regulation of Cellular Zinc Transport

  • Israel Sekler
  • Stefano L. Sensi
  • Michal Hershfinkel
  • William F. Silverman
Proceedings

Abstract

Zinc is an essential cofactor for the activity and folding of up to ten percent of mammalian proteins and can modulate the function of many others. Because of the pleiotropic effects of zinc on every aspect of cell physiology, deficits of cellular zinc content, resulting from zinc deficiency or excessive rise in its cellular concentration, can have catastrophic consequences and are linked to major patho-physiologies including diabetes and stroke. Thus, the concentration of cellular zinc requires establishment of discrete, active cellular gradients. The cellular distribution of zinc into organelles is precisely managed to provide the zinc concentration required by each cell compartment. The complexity of zinc homeostasis is reflected by the surprisingly large variety and number of zinc homeostatic proteins found in virtually every cell compartment. Given their ubiquity and importance, it is surprising that many aspects of the function, regulation, and crosstalk by which zinc transporters operate are poorly understood. In this mini-review, we will focus on the mechanisms and players required for generating physiologically appropriate zinc gradients across the plasma membrane and vesicular compartments. We will also highlight some of the unsolved issues regarding their role in cellular zinc homeostasis.

Notes

Acknowledgments

Thanks to the many members in the zinc community for their invaluable insight and discussions. This work was supported in part by Binational Science Foundation Grant 2001101 (to M. H.), Israel Science Foundation Grant 456/02.1 (to I. S.), German Israel Foundation (GIF, project nr. I-588-99.1/1998 to I.S.), and Israel Science Foundation equipment Grant 456/02.2 (to I. S.).

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Copyright information

© Feinstein Institute for Medical Research 2007

Authors and Affiliations

  • Israel Sekler
    • 1
  • Stefano L. Sensi
    • 2
  • Michal Hershfinkel
    • 3
  • William F. Silverman
    • 3
  1. 1.Department of Physiology, Faculty of Health Science, and The Zlotowski Center for NeuroscienceBen Gurion University of the NegevBeer-ShevaIsrael
  2. 2.Department of Neurology, CESI-Center for research on AgingUniversity G. d’AnnunzioChietiItaly
  3. 3.Department of Morphology, Faculty of Health Science, and The Zlotowski Center for NeuroscienceBen Gurion University of the NegevBeer-ShevaIsrael

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