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Reference - PMID:29529046 - Zinc transporters belonging to the Cation Diffusion Facilitator (CDF) family have complementary roles in transporting zinc out of the cytosol.

Reference summary

PubMed ID
PMID:29529046
Title
Zinc transporters belonging to the Cation Diffusion Facilitator (CDF) family have complementary roles in transporting zinc out of the cytosol.
Authors
Choi S, Hu YM, Corkins ME, Palmer AE, Bird AJ
Citation
PLoS Genet 2018 Mar;14(3):e1007262
Publication year
2018
Abstract
Zinc is an essential trace element that is required for the function of a large number of proteins. As these zinc-binding proteins are found within the cytosol and organelles, all eukaryotes require mechanisms to ensure that zinc is delivered to organelles, even under conditions of zinc deficiency. Although many zinc transporters belonging to the Cation Diffusion Facilitator (CDF) families have well characterized roles in transporting zinc into the lumens of intracellular compartments, relatively little is known about the mechanisms that maintain organelle zinc homeostasis. The fission yeast Schizosaccharomyces pombe is a useful model system to study organelle zinc homeostasis as it expresses three CDF family members that transport zinc out of the cytosol into intracellular compartments: Zhf1, Cis4, and Zrg17. Zhf1 transports zinc into the endoplasmic reticulum, and Cis4 and Zrg17 form a heterodimeric complex that transports zinc into the cis-Golgi. Here we have used the high and low affinity ZapCY zinc-responsive FRET sensors to examine cytosolic zinc levels in yeast mutants that lack each of these CDF proteins. We find that deletion of cis4 or zrg17 leads to higher levels of zinc accumulating in the cytosol under conditions of zinc deficiency, whereas deletion of zhf1 results in zinc accumulating in the cytosol when zinc is not limiting. We also show that the expression of cis4, zrg17, and zhf1 is independent of cellular zinc status. Taken together our results suggest that the Cis4/Zrg17 complex is necessary for zinc transport out of the cytosol under conditions of zinc-deficiency, while Zhf1 plays the dominant role in removing zinc from the cytosol when labile zinc is present. We propose that the properties and/or activities of individual CDF family members are fine-tuned to enable cells to control the flux of zinc out of the cytosol over a broad range of environmental zinc stress.

Annotation

GO biological process

GO:0006882 - intracellular zinc ion homeostasis

Genes:

GO:0071578 - zinc ion import across plasma membrane

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GO:0140209 - zinc ion import into endoplasmic reticulum

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GO:0062111 - zinc ion import into organelle

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GO:0120127 - response to zinc ion starvation

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GO molecular function

GO:0000006 - high-affinity zinc transmembrane transporter activity

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GO:0005385 - zinc ion transmembrane transporter activity

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Multi-locus phenotype

FYPO:0006828 - increased cytosolic zinc level

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FYPO:0001535 - normal cellular zinc level

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Single locus phenotype

FYPO:0001534 - decreased cellular zinc level

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Genotypes:

FYPO:0006827 - decreased cytosolic zinc level

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FYPO:0006334 - decreased RNA level during cellular response to zinc ion starvation

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FYPO:0001355 - decreased vegetative cell population growth

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Genotypes:

FYPO:0006828 - increased cytosolic zinc level

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FYPO:0006830 - normal RNA level during cellular response to replete zinc

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Genotypes:

FYPO:0006829 - normal RNA level during cellular response to zinc ion starvation

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