ArticleMolecular and cellular biology2009
Novel proteolytic processing of the ectodomain of the zinc transporter ZIP4 (SLC39A4) during zinc deficiency is inhibited by acrodermatitis enteropathica mutations.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 130 citations in OpenAlex.
- Human CTR1 Through the Ages: Milestones and Emerging Roles in Disease and Therapy.Biomolecules · 2025Review
- Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.Critical reviews in biochemistry and molecular biology · 2024Review
- Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.International journal of biological sciences · 2024Review
- Review
- Pigmentation and TYRP1 expression are mediated by zinc through the early secretory pathway-resident ZNT proteins.Communications biology · 2023Article
- The LIV-1 Subfamily of Zinc Transporters: From Origins to Present Day Discoveries.International journal of molecular sciences · 2023Review
- Heterologous Expression of Full-Length and Truncated Human ZIP4 Zinc Transporter inBiomolecules · 2022Article
- Sophisticated expression responses of ZNT1 and MT in response to changes in the expression of ZIPs.Scientific reports · 2022Article
- Enhancing effect ofJournal of ginseng research · 2022Article
- Expression Analysis of Zinc Transporters in Nervous Tissue Cells Reveals Neuronal and Synaptic Localization of ZIP4.International journal of molecular sciences · 2021Article
- The Function and Regulation of Zinc in the Brain.Neuroscience · 2021Review
- Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation.Cellular and molecular life sciences : CMLS · 2020Review
- Molecular Basis of Zinc-Dependent Endocytosis of Human ZIP4 Transceptor.Cell reports · 2020Article
- Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation.The Journal of biological chemistry · 2020Article
- Transcription factors and transporters in zinc homeostasis: lessons learned from fungi.Critical reviews in biochemistry and molecular biology · 2020Review
- Elucidating the HInternational journal of molecular sciences · 2020Article
- Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels.The Journal of biological chemistry · 2019Article
- Maintenance of Intestinal Epithelial Homeostasis by Zinc Transporters.Digestive diseases and sciences · 2019Review
- Iron and Zinc Homeostasis and Interactions: Does Enteric Zinc Excretion Cross-Talk with Intestinal Iron Absorption?Nutrients · 2019Review
- The histidine-rich loop in the extracellular domain of ZIP4 binds zinc and plays a role in zinc transport.The Biochemical journal · 2019Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
The zinc transporter ZIP4 (SLC39A4) is mutated in humans with the rare, autosomal recessive genetic disease acrodermatitis enteropathica. In mice, this gene is essential during early embryonic development. ZIP4 is dynamically regulated by multiple posttranscriptional mechanisms, and studies of mouse ZIP4 reported herein reveal that the ectodomain, the extracellular amino-terminal half of the protein, is proteolytically removed during prolonged zinc deficiency while the remaining eight-transmembrane carboxyl-terminal half of the protein is accumulated on the plasma membrane as an abundant form of ZIP4. This novel ZIP4 processing occurs in vivo in the intestine and visceral endoderm, in mouse Hepa cells that express the endogenous Slc39a4 gene and in transfected MDCK and CaCo2 cells, but not HEK293 cells. In transfected MDCK and CaCo2 cells, the ectodomain accumulated and remained associated with membranes when zinc was deficient. ZIP4 cleavage was attenuated by inhibitors of endocytosis, which suggests that the processed protein is recycled back to the plasma membrane and that the ectodomain may be internalized. Ectodomain cleavage is inhibited by acrodermatitis enteropathica mutations near a predicted metalloproteinase cleavage site which is also essential for proper ectodomain cleavage, and overexpression of processed ZIP4 or ZIP4 with ectodomain truncations rendered the mouse Mt1 gene hypersensitive to zinc. These finding suggest that the processing of ZIP4 may represent a significant regulatory mechanism controlling its function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.