Requirement of Zinc Transporter SLC39A7/ZIP7 for Dermal Development to Fine-Tune Endoplasmic Reticulum Function by Regulating Protein Disulfide Isomerase.

The Journal of investigative dermatology 2017 Aug

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Skin is the first area that manifests zinc deficiency. However, the molecular mechanisms by which zinc homeostasis affects skin development remain largely unknown. Here, we show that zinc-regulation transporter-/iron-regulation transporter-like protein 7 (ZIP7) localized to the endoplasmic reticulum plays critical roles in connective tissue development. Mice lacking the Slc39a7/Zip7 gene in collagen 1-expressing tissue exhibited dermal dysplasia. Ablation of ZIP7 in mesenchymal stem cells inhibited cell proliferation thereby preventing proper dermis formation, indicating that ZIP7 is required for dermal development. We also found that mesenchymal stem cells lacking ZIP7 accumulated zinc in the endoplasmic reticulum, which triggered zinc-dependent aggregation and inhibition of protein disulfide isomerase, leading to endoplasmic reticulum dysfunction. These results suggest that ZIP7 is necessary for endoplasmic reticulum function in mesenchymal stem cells and, as such, is essential for dermal development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Bum-Ho Bin, Jinhyuk Bhin, Juyeon Seo, Se-Young Kim, Eunyoung Lee, Kyuhee Park, Dong-Hwa Choi, Teruhisa Takagishi, Takafumi Hara, Daehee Hwang, Haruhiko Koseki, Yoshinobu Asada, Shinji Shimoda, Kenji Mishima, Toshiyuki Fukada. Requirement of Zinc Transporter SLC39A7/ZIP7 for Dermal Development to Fine-Tune Endoplasmic Reticulum Function by Regulating Protein Disulfide Isomerase. The Journal of investigative dermatology. 2017 Aug;137(8):1682-1691