SREL Reprint #3063

Evidence That the ZNT3 Protein Controls the Total Amount of Elemental Zinc in Synaptic Vesicles

David H. Linkous1, Jane M. Flinn1, Jae Y. Koh2, Antonio Lanzirotti3,4, Paul M. Bertsch5,
Blair F. Jones6, Leonard J. Giblin7, and Christopher J. Frederickson7

1Department of Psychology, George Mason University, Fairfax, Virginia
2Department of Neurology, University of Ulsan College of Medicine, Poongnapdong, Songpagu, Seoul, South Korea
3Consortium for Advanced Radiation Sources, University of Chicago, Chicago, Illinois
4National Synchrotron Light Source, Brookhaven National Laboratory, Upton, New York
5Savannah River Ecology Laboratory, University of Georgia, Aiken, South Carolina
6United States Geological Survey, Reston, Virginia
7NeuroBioTex, Inc., Galveston, Texas

Abstract: The ZNT3 protein decorates the presynaptic vesicles of central neurons harboring vesicular zinc, and deletion of this protein removes staining for zinc. However, it has been unclear whether only histochemically reactive zinc is lacking or if, indeed, total elemental zinc is missing from neurons lacking the Slc30a3 gene, which encodes the ZNT3 protein. The limitations of conventional histochemical procedures have contributed to this enigma. However, a novel technique, microprobe synchrotron X-ray fluorescence, reveals that the normal 2- to 3-fold elevation of zinc concentration normally present in the hippocampal
mossy fibers is absent in Slc30a3 knockout (ZNT3) mice. Thus, the ZNT3 protein evidently controls not only the “stainability” but also the actual mass of zinc in mossy-fiber synaptic vesicles. This work thus confirms the metal-transporting role of the ZNT3 protein in the brain.

Key words: mossy fibers, ZNT3, glutamate, zinc release, hilus, X-ray, fluorescence, knockout

SREL Reprint #3063

Linkous, D. H., J. M. Flinn, J. Y. Koh, A. Lanzirotti, P. M. Bertsch, B. F. Jones, L. J. Giblin, and C. J. Frederickson. 2008. Evidence That the ZNT3 Protein Controls the Total Amount of Elemental Zinc in Synaptic Vesicles. Journal of Histochemistry and Cytochemistry 56(1): 3-6.

This information was provided by the University of Georgia's Savannah River Ecology Laboratory (srel.uga.edu).