Ctr2 Regulates Mast Cell Maturation by Affecting the Storage and Expression of Tryptase and Proteoglycans

The Journal of Immunology : Official Journal of the American Association of Immunologists
Helena OhrvikGunnar Pejler

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...Continue Reading

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Citations

May 12, 2017·Cell Death & Disease·Gunnar PejlerHelena Öhrvik
Dec 3, 2016·Glycoconjugate Journal·B MulloyC P Page
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Oct 26, 2018·Emerging Topics in Life Sciences·Bryan E Thacker, Susan T Sharfstein
Mar 7, 2021·International Journal of Molecular Sciences·Bettina SprinzlGregor Hoermann
Aug 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·May T MaungTeresita Padilla-Benavides
Nov 5, 2021·Journal of Cell Science·Svetlana Lutsenko

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