Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels

Nishito, Yukina; Kambe, Taiho

doi:10.1074/jbc.ra119.010227

Cited by 86 publications

(91 citation statements)

References 56 publications

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“…Likewise, it is known that cellular zinc levels regulate ZnT1 expression via metal regulatory transcription factor 1 (MTF1) [ 30 ]. During zinc deficiency, membrane-bound ZnT1 is degraded [ 31 ] and its mRNA levels were described to decrease in mouse pancreas [ 29 ] as well as in the intestine of weaning rats [ 32 ]. Accordingly, gene expression changes of these transporters in post-confluent zinc-restricted goblet cells might be another reason for their enhanced zinc uptake ( Figure 3 B).…”

Section: Resultsmentioning

confidence: 99%

Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells

Maares

Keil

Straubing

et al. 2020

IJMS

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Approximately 1 billion people worldwide suffer from zinc deficiency, with severe consequences for their well-being, such as critically impaired intestinal health. In addition to an extreme degeneration of the intestinal epithelium, the intestinal mucus is seriously disturbed in zinc-deficient (ZD) animals. The underlying cellular processes as well as the relevance of zinc for the mucin-producing goblet cells, however, remain unknown. To this end, this study examines the impact of zinc deficiency on the synthesis, production, and secretion of intestinal mucins as well as on the zinc homeostasis of goblet cells using the in vitro goblet cell model HT-29-MTX. Zinc deprivation reduced their cellular zinc content, changed expression of the intestinal zinc transporters ZIP-4, ZIP-5, and ZnT1 and increased their zinc absorption ability, outlining the regulatory mechanisms of zinc homeostasis in goblet cells. Synthesis and secretion of mucins were severely disturbed during zinc deficiency, affecting both MUC2 and MUC5AC mRNA expression with ongoing cell differentiation. A lack of zinc perturbed mucin synthesis predominantly on the post-translational level, as ZD cells produced shorter O-glycans and the main O-glycan pattern was shifted in favor of core-3-based mucins. The expression of glycosyltransferases that determine the formation of core 1-4 O-glycans was altered in zinc deficiency. In particular, B3GNT6 mRNA catalyzing core 3 formation was elevated and C2GNT1 and C2GNT3 elongating core 1 were downregulated in ZD cells. These novel insights into the molecular mechanisms impairing intestinal mucus stability during zinc deficiency demonstrate the essentiality of zinc for the formation and maintenance of this physical barrier.

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Section: Resultsmentioning

confidence: 99%

Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells

Maares

Keil

Straubing

et al. 2020

IJMS

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“…MTF-1 directly senses cytoplasmic zinc concentrations in enterocytes and regulates ZnT-1 expression, which ensures sufficient capacities for export of the cation into the portal blood and controls intracellular zinc-free levels [108]. Furthermore, aside of its transcriptional regulation, the zinc-regulated surface accumulation of ZnT-1 might also be facilitated on a post-transcriptional level, whereas, during zinc deficiency, the protein is degraded via lysosomal and proteasomal pathways [138]. Nevertheless, in vivo data for basolateral ZnT-1 during zinc excess and deficiency are contradictory and scarce regarding its differential expression in humans.…”

Section: Enterocyte Zinc Homeostasis and Regulation Of Intestinal Zinmentioning

confidence: 99%

A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models

2020

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Zinc absorption in the small intestine is one of the main mechanisms regulating the systemic homeostasis of this essential trace element. This review summarizes the key aspects of human zinc homeostasis and distribution. In particular, current knowledge on human intestinal zinc absorption and the influence of diet-derived factors on bioaccessibility and bioavailability as well as intrinsic luminal and basolateral factors with an impact on zinc uptake are discussed. Their investigation is increasingly performed using in vitro cellular intestinal models, which are continually being refined and keep gaining importance for studying zinc uptake and transport via the human intestinal epithelium. The vast majority of these models is based on the human intestinal cell line Caco-2 in combination with other relevant components of the intestinal epithelium, such as mucin-secreting goblet cells and in vitro digestion models, and applying improved compositions of apical and basolateral media to mimic the in vivo situation as closely as possible. Particular emphasis is placed on summarizing previous applications as well as key results of these models, comparing their results to data obtained in humans, and discussing their advantages and limitations.

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“…SLC30A1 (ZnT1) is expressed at the plasma membrane, where it drives the efflux of zinc into extracellular space. The expression of this transporter is tightly regulated, with both expression and plasma membrane localization increasing in response to higher zinc concentrations in the cytoplasm [467,468].…”

Section: Slc30/slc39mentioning

confidence: 99%

A guide to plasma membrane solute carrier proteins

2020

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This review aims to serve as an introduction to the solute carrier proteins (SLC) superfamily of transporter proteins and their roles in human cells. The SLC superfamily currently includes 458 transport proteins in 65 families that carry a wide variety of substances across cellular membranes. While members of this superfamily are found throughout cellular organelles, this review focuses on transporters expressed at the plasma membrane. At the cell surface, SLC proteins may be viewed as gatekeepers of the cellular milieu, dynamically responding to different metabolic states. With altered metabolism being one of the hallmarks of cancer, we also briefly review the roles that surface SLC proteins play in the development and progression of cancer through their influence on regulating metabolism and environmental conditions.

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Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels

Cited by 86 publications

References 56 publications

Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells

Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells

A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models

A guide to plasma membrane solute carrier proteins

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