ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Ctr2 Regulates Mast Cell Maturation by Affecting the Storage and Expression of Tryptase and Proteoglycans.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- ATP7B-maintained copper stores in myeloid progenitors are required for functional maturation of neutrophils.Cell reports · 2026Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Transcriptional Responses of Copper-Transport-Related GenesInternational journal of molecular sciences · 2022Article
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease.Respiratory research · 2021Review
- Genetic Regulation of Tryptase Production and Clinical Impact: Hereditary Alpha Tryptasemia, Mastocytosis and Beyond.International journal of molecular sciences · 2021Review
- Lysosomotropic challenge of mast cells causes intra-granular reactive oxygen species production.Cell death discovery · 2019Article
- Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin as a Nutritive Source of Copper: Overview of the Current Data.Nutrients · 2018Review
- Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Mast cell glycosaminoglycans.Glycoconjugate journal · 2017Review
- Acidic pH is essential for maintaining mast cell secretory granule homeostasis.Cell death & disease · 2017Article
- Copper transporters and chaperones CTR1, CTR2, ATOX1, and CCS as determinants of cisplatin sensitivity.Metallomics : integrated biometal science · 2016Article
- Copper trafficking to the secretory pathway.Metallomics : integrated biometal science · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Copper (Cu) is essential for multiple cellular functions. Cellular uptake of Cu(+) is carried out by the Ctr1 high-affinity Cu transporter. The mobilization of endosomal Cu pools is regulated by a protein structurally similar to Ctr1, called Ctr2. It was recently shown that ablation of Ctr2 caused an increase in the concentration of Cu localized to endolysosomes. However, the biological significance of excess endolysosomal Cu accumulation has not been assessed. In this study, we addressed this issue by investigating the impact of Ctr2 deficiency on mast cells, a cell type unusually rich in endolysosomal organelles (secretory granules). We show that Ctr2(-/-) mast cells have increased intracellular Cu concentrations and that the absence of Ctr2 results in increased metachromatic staining, the latter indicating an impact of Ctr2 on the storage of proteoglycans in the secretory granules. In agreement with this, the absence of Ctr2 caused a skewed ratio between proteoglycans of heparin and chondroitin sulfate type, with increased amounts of heparin accompanied by a reduction of chondroitin sulfate. Moreover, transmission electron microscopy analysis revealed a higher number of electron-dense granules in Ctr2(-/-) mast cells than in wild-type cells. The increase in granular staining and heparin content is compatible with an impact of Ctr2 on mast cell maturation and, in support of this, the absence of Ctr2 resulted in markedly increased mRNA expression, storage, and enzymatic activity of tryptase. Taken together, the present study introduces Ctr2 and Cu as novel actors in the regulation of mast cell maturation and granule homeostasis.
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Registered trials
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