Mechanism and regulation of cellular zinc transport.
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.
Sekler
Israel
I
Department of Physiology, Faculty of Health Science, and The Zlotowski Center for Neuroscience, Ben Gurion University of the Negev, POB 653, Beer-Sheva, Israel. sekler@bgu.ac.il
Sensi
Stefano L
SL
Hershfinkel
Michal
M
Silverman
William F
WF
D000818:Animals; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D015032:Zinc / Q000378:metabolism*
D027682:Cation Transport Proteins; D015032:Zinc