title: Decreased hemojuvelin protein levels in mask mice lacking matriptase-2-dependent proteolytic activity.
abstract: Matriptase-2, a membrane protein encoded by the Tmprss6 gene, is a negative regulator of hepcidin expression. Although matriptase-2 has been proposed to cleave membrane hemojuvelin, we have recently found decreased hemojuvelin protein levels in Tmprss6 -/- mice. The purpose of this study was to confirm this observation by determining hemojuvelin protein levels in another strain of mice with disrupted Tmprss6 gene, and to determine the effect of matriptase-2 deficiency on the expression of other membrane proteins participating in the bone morphogenetic protein signal transduction. Mask mice, which lack the proteolytic domain of matriptase-2, displayed decreased liver hemojuvelin protein content, while Id1 mRNA level, an indicator of hemojuvelin-dependent signal transduction, was increased. Protein levels of bone morphogenetic protein receptors Alk3 and Acvr2a were unchanged, and transferrin receptor 2 and neogenin protein levels were slightly decreased. The results confirm that the loss of matriptase-2 increases bone morphogenetic protein-dependent signaling, while paradoxically decreasing liver hemojuvelin protein content. The regulation of transferrin receptor 2 protein levels by transferrin saturation was not affected in mask mice. How the loss of matriptase-2 proteolytic activity leads to decreased hemojuvelin protein levels is at present unclear.
authors.affiliation: Institute of Pathophysiology, First Faculty of Medicine, Charles University, Prague, Czech Republic. jkri@lf1.cuni.cz
authors.forename: J
authors.initials: J
authors.lastname: Frýdlová
authors.forename: Y
authors.initials: Y
authors.lastname: Fujikura
authors.forename: M
authors.initials: M
authors.lastname: Vokurka
authors.forename: E
authors.initials: E
authors.lastname: Nečas
authors.forename: J
authors.initials: J
authors.lastname: Krijt
mesh_terms: D030301:Activin Receptors, Type II / Q000378:metabolism; D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D058851:GPI-Linked Proteins; D000071020:Hemochromatosis Protein; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D000090463:Iron Deficiencies; D007505:Iron-Dextran Complex / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000235:genetics
chemical_list: D058851:GPI-Linked Proteins; C504414:HJV protein, mouse; D000071020:Hemochromatosis Protein; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D008565:Membrane Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; C503641:TFR2 protein, mouse; C091279:neogenin; D007505:Iron-Dextran Complex; D030301:Activin Receptors, Type II; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; C425585:activin receptor type II-A; D012697:Serine Endopeptidases; C467801:matriptase 2