ZnT3: a zinc transporter active in several organs

Smidt, Kamille; Rungby, Jørgen

doi:10.1007/s10534-011-9490-x

Cited by 33 publications

(17 citation statements)

References 67 publications

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“…This Zn 2+ transporter is also expressed in β-cells [11,14,49,50]. The increase in ZnT-3 gene expression observed in the present study is consistent with our previous finding [11] that ZnT-3 is upregulated during stressful conditions (Figure 6A).…”

Section: Discussionsupporting

confidence: 93%

Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

et al. 2014

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BackgroundZinc is essential for the activities of pancreatic β-cells, especially insulin storage and secretion. Insulin secretion leads to co-release of zinc which contributes to the paracrine communication in the pancreatic islets. Zinc-transporting proteins (zinc-regulated transporter, iron-regulated transporter-like proteins [ZIPs] and zinc transporters [ZnTs]) and metal-buffering proteins (metallothioneins, MTs) tightly regulate intracellular zinc homeostasis. The present study investigated how modulation of cellular zinc availability affects β-cell function using INS-1E cells.ResultsUsing INS-1E cells, we found that zinc supplementation and zinc chelation had significant effects on insulin content and insulin secretion. Supplemental zinc within the physiological concentration range induced insulin secretion. Insulin content was reduced by zinc chelation with N,N,N’,N-tektrakis(2-pyridylmethyl)-ethylenediamine. The changes in intracellular insulin content following exposure to various concentrations of zinc were reflected by changes in the expression patterns of MT-1A, ZnT-8, ZnT-5, and ZnT-3. Furthermore, high zinc concentrations induced cell necrosis while zinc chelation induced apoptosis. Finally, cell proliferation was sensitive to changes in zinc the concentration.ConclusionThese results indicate that the β-cell-like function and survival of INS-1E cells are dependent on the surrounding zinc concentrations. Our results suggest that regulation of zinc homeostasis could represent a pharmacological target.

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Section: Discussionsupporting

confidence: 93%

Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

et al. 2014

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“…Whereas mouse ZnT3 is expressed in several organs (Palmiter et al . ; Smidt and Rungby ), mouse SV31 is exclusively expressed in brain (Burré et al . ).…”

Section: Discussionmentioning

confidence: 99%

“…SV31 shares approximately 20% sequence homology and structural similarity with murine ZnT3, a vesicular Zn 2+ transporter with eight mammalian paralogs (Kambe 2012). Whereas mouse ZnT3 is expressed in several organs (Palmiter et al 1996;Smidt and Rungby 2012), mouse SV31 is exclusively expressed in brain . Neither the location of ZnT3 protein nor mRNA in the brain coincides with the distribution of SV31 .…”

Section: Discussionmentioning

confidence: 99%

The synaptic vesicle protein SV31 assembles into a dimer and transports Zn²⁺

Waberer

Henrich

Peetz

et al. 2016

Journal of Neurochemistry

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The integral synaptic vesicle protein SV31 has been shown to bind divalent cations. Here, we demonstrate that SV31 protein synthesized within a cell-free system binds Zn and to a lower extent Ni and Cu ions. Expression with Zn stabilized the protein and increased solubility. SV31 was preferentially monomeric in detergent and revealed specific binding of Zn . When co-translationally inserted into defined nanodisc bilayers, SV31 assembled into dimeric complexes, resulting in increased binding of Zn . Putative Zn -binding motifs within SV31 comprise aspartic acid and histidine residues. Site-directed mutagenesis of two conserved aspartic acid residues leads to a potent decrease in Zn binding but did not affect dimerization. Chemical modification of histidine residues abolished some of the Zn -binding capacity. We demonstrate proton-dependent transport of Zn as by accumulation of fluorescent FluoZin-1 inside of SV31-containing proteoliposomes. Transport activity has a K value of 44.3 μM and required external Zn and internal acidic pH. Our results demonstrate that the synaptic vesicle-integral protein SV31 functions as a proton-dependent Zn transporter. SV31 may attribute specific and yet undiscovered functions to subsets of synapses.

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“…SLC30A3, also known as ZnT3, serves to transport Zn into the pre-synaptic vesicles to be later released during neuronal transmission2526. SLC30A3 is also expressed in pancreatic β-cells and plays a role in insulin production27.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Zinc-Exporters Expression in Prostate Cancer

Singh

Malas

Tydrick

et al. 2016

Sci Rep

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Maintaining optimal intracellular zinc (Zn) concentration is crucial for critical cellular functions. Depleted Zn has been associated with prostate cancer (PCa) progression. Solute carrier family 30 (SLC30A) proteins maintain cytoplasmic Zn balance by exporting Zn out to the extracellular space or by sequestering cytoplasmic Zn into intracellular compartments. In this study, we determined the involvement of Zn-exporters, SLC30A 1–10 in PCa, in the context of racial health disparity in human PCa samples obtained from European-American (EA) and African-American (AA) populations. We also analyzed the levels of Zn-exporters in a panel of PCa cells derived from EA and AA populations. We further explored the expression profile of Zn-exporters in PCa using Oncomine database. Zn-exporters were found to be differentially expressed at the mRNA level, with a significant upregulation of SLC30A1, SLC30A9 and SLC30A10, and downregulation of SLC30A5 and SLC30A6 in PCa, compared to benign prostate. Moreover, Ingenuity Pathway analysis revealed several interactions of Zn-exporters with certain tumor suppressor and promoter proteins known to be modulated in PCa. Our study provides an insight regarding Zn-exporters in PCa, which may open new avenues for future studies aimed at enhancing the levels of Zn by modulating Zn-transporters via pharmacological means.

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ZnT3: a zinc transporter active in several organs

Cited by 33 publications

References 67 publications

Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

The synaptic vesicle protein SV31 assembles into a dimer and transports Zn²⁺

Analysis of Zinc-Exporters Expression in Prostate Cancer

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ZnT3: a zinc transporter active in several organs

Cited by 33 publications

References 67 publications

Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

The synaptic vesicle protein SV31 assembles into a dimer and transports Zn2+

Analysis of Zinc-Exporters Expression in Prostate Cancer

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The synaptic vesicle protein SV31 assembles into a dimer and transports Zn²⁺