ArticleThe Journal of biological chemistry2012
Neogenin interacts with matriptase-2 to facilitate hemojuvelin cleavage.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Pooled it
- The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Article
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies inInternational journal of molecular sciences · 2021Article
- Article
- Regulation of Iron Homeostasis and Related Diseases.Mediators of inflammation · 2020Review
- Rgma-Induced Neo1 Proteolysis Promotes Neural Tube Morphogenesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Hepatic heparan sulfate is a master regulator of hepcidin expression and iron homeostasis in human hepatocytes and mice.The Journal of biological chemistry · 2019Article
- The Functional Versatility of Transferrin Receptor 2 and Its Therapeutic Value.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Differential regulation of hepcidin in cancer and non-cancer tissues and its clinical implications.Experimental & molecular medicine · 2018Review
- Matriptase-2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway.The Journal of biological chemistry · 2017Article
- Regulation of the Iron Homeostatic Hormone Hepcidin.Advances in nutrition (Bethesda, Md.) · 2017Review
- Endogenous DNA Damage Leads to p53-Independent Deficits in Replicative Fitness in Fetal Murine Fancd2Stem cell reports · 2016Article
- Neogenin Facilitates the Induction of Hepcidin Expression by Hemojuvelin in the Liver.The Journal of biological chemistry · 2016Article
- Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats.PloS one · 2016Article
- Identification of TMPRSS6 cleavage sites of hemojuvelin.Journal of cellular and molecular medicine · 2015Article
- Identification of the soluble form of tyrosine kinase receptor Axl as a potential biomarker for intracranial aneurysm rupture.BMC neurology · 2015Article
- Low intracellular iron increases the stability of matriptase-2.The Journal of biological chemistry · 2015Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hemojuvelin (HJV) and matriptase-2 (MT2) are co-expressed in hepatocytes, and both are essential for systemic iron homeostasis. HJV is a glycosylphosphatidylinositol-linked membrane protein that acts as a co-receptor for bone morphogenetic proteins to induce hepcidin expression. MT2 regulates the levels of membrane-bound HJV in hepatocytes by binding to and cleaving HJV into an inactive soluble form that is released from cells. HJV also interacts with neogenin, a ubiquitously expressed transmembrane protein with multiple functions. In this study, we showed that neogenin interacted with MT2 as well as with HJV and facilitated the cleavage of HJV by MT2. In contrast, neogenin was not cleaved by MT2, indicating some degree of specificity by MT2. Down-regulation of neogenin with siRNA increased the amount of MT2 and HJV on the plasma membrane, suggesting a lack of neogenin involvement in their trafficking to the cell surface. The increase in MT2 and HJV upon neogenin knockdown was likely due to the inhibition of cell surface MT2 and HJV internalization. Analysis of the Asn-linked oligosaccharides showed that MT2 cleavage of cell surface HJV was coupled to a transition from high mannose oligosaccharides to complex oligosaccharides on HJV. These results suggest that neogenin forms a ternary complex with both MT2 and HJV at the plasma membrane. The complex facilitates HJV cleavage by MT2, and release of the cleaved HJV from the cell occurs after a retrograde trafficking through the TGN/Golgi compartments.
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Registered trials
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.