Functionally impaired isoforms regulate TMPRSS6 proteolytic activity.
TMPRSS6 is a type II transmembrane serine protease involved in iron homeostasis expressed as 4 isoforms in humans. TMPRSS6 isoform 2 downregulates hepcidin production by cleaving hemojuvelin and other surface proteins of hepatocytes. The functions of catalytically impaired isoforms 3 and 4 are still...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0273825&type=printable |
| _version_ | 1826545848052350976 |
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| author | Sébastien P Dion Antoine Désilets Gabriel Lemieux Richard Leduc |
| author_facet | Sébastien P Dion Antoine Désilets Gabriel Lemieux Richard Leduc |
| author_sort | Sébastien P Dion |
| collection | DOAJ |
| description | TMPRSS6 is a type II transmembrane serine protease involved in iron homeostasis expressed as 4 isoforms in humans. TMPRSS6 isoform 2 downregulates hepcidin production by cleaving hemojuvelin and other surface proteins of hepatocytes. The functions of catalytically impaired isoforms 3 and 4 are still unknown. Here we demonstrate that TMPRSS6 isoforms 3 and 4 reduce the proteolytic activity of isoform 2 and uncover the ability of isoforms to interact. Moreover, we identified 49 potential protein partners common to TMPRSS6 isoforms, including TfR1, known to be involved in iron regulation. By co-expressing TMPRSS6 and TfR1, we show that TfR1 is cleaved and shed from the cell surface. Further, we demonstrate that TMPRSS6 isoforms 3 and 4 behave as dominant negative. |
| first_indexed | 2024-04-12T18:51:01Z |
| format | Article |
| id | doaj.art-59be08b264514d2e81747bc264b43c0a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T05:24:23Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-59be08b264514d2e81747bc264b43c0a2025-03-06T05:31:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01178e027382510.1371/journal.pone.0273825Functionally impaired isoforms regulate TMPRSS6 proteolytic activity.Sébastien P DionAntoine DésiletsGabriel LemieuxRichard LeducTMPRSS6 is a type II transmembrane serine protease involved in iron homeostasis expressed as 4 isoforms in humans. TMPRSS6 isoform 2 downregulates hepcidin production by cleaving hemojuvelin and other surface proteins of hepatocytes. The functions of catalytically impaired isoforms 3 and 4 are still unknown. Here we demonstrate that TMPRSS6 isoforms 3 and 4 reduce the proteolytic activity of isoform 2 and uncover the ability of isoforms to interact. Moreover, we identified 49 potential protein partners common to TMPRSS6 isoforms, including TfR1, known to be involved in iron regulation. By co-expressing TMPRSS6 and TfR1, we show that TfR1 is cleaved and shed from the cell surface. Further, we demonstrate that TMPRSS6 isoforms 3 and 4 behave as dominant negative.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0273825&type=printable |
| spellingShingle | Sébastien P Dion Antoine Désilets Gabriel Lemieux Richard Leduc Functionally impaired isoforms regulate TMPRSS6 proteolytic activity. PLoS ONE |
| title | Functionally impaired isoforms regulate TMPRSS6 proteolytic activity. |
| title_full | Functionally impaired isoforms regulate TMPRSS6 proteolytic activity. |
| title_fullStr | Functionally impaired isoforms regulate TMPRSS6 proteolytic activity. |
| title_full_unstemmed | Functionally impaired isoforms regulate TMPRSS6 proteolytic activity. |
| title_short | Functionally impaired isoforms regulate TMPRSS6 proteolytic activity. |
| title_sort | functionally impaired isoforms regulate tmprss6 proteolytic activity |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0273825&type=printable |
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