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

Title
Requirement of Zinc Transporter SLC39A7/ZIP7 for Dermal Development to Fine-Tune Endoplasmic Reticulum Function by Regulating Protein Disulfide Isomerase
Authors
Bin, Bum-HoBhin, JinhyukSeo, JuyeonKim, Se-YoungLee, EunyoungPark, KyuheeChoi, Dong-HwaTakagishi, TeruhisaHara, TakafumiHwang, DaeheeKoseki, HaruhikoAsada, YoshinobuShimoda, ShinjiMishima, KenjiFukada, Toshiyuki
DGIST Authors
Hwang, Daehee
Issue Date
2017-08
Citation
Journal of Investigative Dermatology, 137(8), 1682-1691
Type
Article
Article Type
Article
Keywords
Acrodermatitis EnteropathicaCellsConnective TissueEhlers Danlos SyndromeGrowthIn VivoLIV 1 SubfamilyMicePoint MutationsSignaling Pathways
ISSN
0022-202X
Abstract
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. © 2017 The Authors
URI
http://hdl.handle.net/20.500.11750/4403
DOI
10.1016/j.jid.2017.03.031
Publisher
Elsevier B.V.
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
New BiologyETC1. Journal Articles


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