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. 2022 May 5;12:7334. doi: 10.1038/s41598-022-10925-2

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Model depicting ZIP-driven ZNT1 expression for homeostatic control. (A) Model showing ZIP-driven ZNT1 expression in generic cells. Increased expression of cell-surface ZIPs results in increased zinc content in the cytosol, which leads to the enhanced expression of ZNT1 and the subsequent dampening of increases in cytosolic zinc concentration (upper). Conversely, decreased expression of cell-surface ZIPs causes a decrease in the zinc content in the cytosol, which results in the decreased expression of ZNT1 and thus the maintenance around a homeostatic setpoint at a specific concentration in each cell type (lower). (B) Prediction model showing ZIP4-driven ZNT1 expression in the zinc-absorption process in enterocytes. Increased ZIP4 expression on the apical surface results in enhanced zinc content in the cytosol, which, in turn, leads to the upregulation of ZNT1 expression and thereby enables efficient export of zinc on the basolateral side into the blood stream (upper). Conversely, decreased ZIP4 expression on the apical surface causes the opposite responses through a decrease in the zinc content in the cytosol and decreased ZNT1 expression, and thus leads to reduced zinc export (lower).