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J. Biol. Chem., Vol. 278, Issue 17, 15065-15072, April 25, 2003
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From the Departments of Zinc is an essential nutrient but toxic to cells
with overaccumulation. For this reason, intracellular zinc levels are
tightly controlled. In the yeast Saccharomyces cerevisiae,
the Zrc1 and Cot1 proteins have been implicated in the storage and
detoxification of excess zinc in the vacuole. Surprisingly,
transcription of ZRC1 is induced in zinc-limited cells by
the zinc-responsive transcription factor Zap1. We show here that this
increase in ZRC1 expression is a novel mechanism of zinc
homeostasis and stress tolerance. Zinc-limited cells also express high
levels of the plasma membrane zinc uptake transporters. As a
consequence, when zinc-limited cells are resupplied with small amounts
of zinc, large quantities quickly accumulate in the cell, a condition
we refer to as "zinc shock." We show here that ZRC1 and
its induction in zinc-limited cells are required for resistance to this
zinc shock. Experiments using the zinc-responsive fluorophore FuraZin-1
as an indicator of vacuolar zinc levels indicated that Zrc1 is required
for the rapid transport of zinc into the vacuole during zinc shock. We also present evidence that cytosolic zinc rises to higher levels in
cells unable to sequester this excess zinc. Thus, the increase in ZRC1 expression occurs prior to the zinc shock stress
for which this induction is important. We propose that this
"proactive" strategy of homeostatic regulation, such as we document
here for ZRC1, may represent a common but largely
unrecognized phenomenon.
Induction of the ZRC1 Metal Tolerance Gene in
Zinc-limited Yeast Confers Resistance to Zinc Shock*
,¶
Nutritional Sciences and
§ Physiology, University of Missouri, Columbia, Missouri
65211
*
This work was supported by National Institutes of Health
Grants GM56285 (to D. J. E.) and DK37512 (to M. A. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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