ArticleScientific reports2022
Sophisticated expression responses of ZNT1 and MT in response to changes in the expression of ZIPs.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Functional characterization of a novel ZIP8 variant causing impaired manganese homeostasis and congenital disorders of glycosylation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Unveiling the prognostic and therapeutic landscape of the zinc transporter protein SLC39A family in colorectal cancer through multi-omics and machine learning approaches.Clinical and experimental medicine · 2026Article
- ZIP-ZnT1 complexes mediate a local ZnCellular and molecular life sciences : CMLS · 2026Article
- Metal-related cell death and its application in pancreatic cancer.Expert reviews in molecular medicine · 2025Review
- Modulation of ZnT-1 by Let7a unveils a therapeutic potential in amyotrophic lateral sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Dietary Dihydromyricetin Zinc Chelate Supplementation Improves the Intestinal Health of Magang Geese.Biological trace element research · 2024Article
- Modulation of Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters.Biomolecules · 2024Review
- The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications.Frontiers in pharmacology · 2024Review
- Effects of Different Dietary Zinc (Zn) Sources on Growth Performance, Zn Metabolism, and Intestinal Health of Grass Carp.Antioxidants (Basel, Switzerland) · 2023Article
- Pigmentation and TYRP1 expression are mediated by zinc through the early secretory pathway-resident ZNT proteins.Communications biology · 2023Article
- Zinc's Association with the CmPn/CmP Signaling Network in Breast Cancer Tumorigenesis.Biomolecules · 2022Review
- Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A.Neuroscience letters · 2022Article
- Investigating the Role of Zinc in Atherosclerosis: A Review.Biomolecules · 2022Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The zinc homeostatic proteins Zn transporter 1 (ZNT1) and metallothionein (MT) function in dampening increases in cytosolic zinc concentrations. Conversely, the expression of ZNT1 and MT is expected to be suppressed during decreases in cytosolic zinc concentrations. Thus, ZNT1/MT homeostatic responses are considered to be essential for maintaining cellular zinc homeostasis because cellular zinc concentrations are readily altered by changes in the expression of several Zrt-/Irt-like proteins (ZIPs) under both physiological and pathological conditions. However, this notion remains to be tested experimentally. Here, we investigated the aforementioned homeostatic process by analyzing ZNT1 and MT protein expression in response to ZIP expression. Overexpression of cell-surface-localized ZIPs, such as ZIP4 and ZIP5, increased the cellular zinc content, which caused an increase in the expression of cell-surface ZNT1 and cytosolic MT in the absence of zinc supplementation in the culture medium. By contrast, elimination of the overexpressed ZIP4 and ZIP5 resulted in decreased expression of ZNT1 but not MT, which suggests that differential regulation of ZNT1 and MT expression at the protein level underlies the homeostatic responses necessary for zinc metabolism under certain conditions. Moreover, increased expression of apically localized ZIP4 facilitated basolateral ZNT1 expression in polarized cells, which indicates that such a coordinated expression mechanism is crucial for vectorial transcellular transport. Our results provide novel insights into the physiological maintenance of cellular zinc homeostasis in response to alterations in cytosolic zinc concentrations caused by changes in the expression of ZIPs.
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