Post-translation Control of Nramp Metal Transport in Yeast
ROLE OF METAL IONS AND THE BSD2 GENE*
- From the Department of Environmental Health Sciences, Johns Hopkins University, School of Public Health, Baltimore, Maryland 21205
Abstract
The Saccharomyces cerevisiae SMF1gene encodes a member of the well conserved family of Nramp metal transport proteins. Previously, we determined that heavy metal uptake by Smf1p was down-regulated by the product of the S. cerevisiae BSD2 gene. We now demonstrate that this regulation occurs at the level of protein stability. In wild type strains, the bulk of Smf1p is normally directed to the vacuole and is rapidly degraded by vacuolar proteases in a PEP4-dependent manner. Inbsd2Δ mutants, Smf1p fails to enter the vacuole, and the Nramp protein is stabilized. Metal ions themselves play an important role in the post-translational regulation of Smf1p. The depletion of heavy metals from the growth medium effects stabilization of Smf1p and additionally results in accumulation of this transporter at the cell surface. Supplementation of manganese alone is sufficient to trigger rapid degradation of Smf1p in a Bsd2p-dependent manner. Together the action of Bsd2p and metal ions provide a rapid and effective means for controlling Nramp metal transport in response to environmental changes.
Footnotes
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↵* This work was funded by the Johns Hopkins University NIEHS Center, National Institutes of Health, and by National Institutes of Health Grant ES 08996 (to V. C. C.).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.
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↵‡ Supported by National Institutes of Health training grant ES 07141.
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↵§ To whom correspondence should be addressed: Johns Hopkins University, 615 N. Wolfe St., Rm. 7032, Baltimore, MD 21205. Tel.: 410-955-3029; Fax: 410–955-0116; E-mail: vculotta{at}jhsph.edu.
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↵2 X. F. Liu and V. C. Culotta, manuscript submitted.
- Abbreviations:
- ER
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endoplasmic reticulum
- MDM
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metal-depleted minimal defined medium
- PCR
-
polymerase chain reaction
- SD
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synthetic minimal medium containing dextrose
- FITC
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fluorescein isothiocyanate
- DAPI
-
4,6-diamidino-2-phenylindole
- HA
-
hemagglutinin
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- Received October 28, 1998.
- Revision received December 9, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
