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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
PloS one - 17(2022), 8 vom: 14., Seite e0273825 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dion, Sébastien P [VerfasserIn] |
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| Links: |
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| Themen: |
E1UOL152H7 |
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| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 14.09.2022 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0273825 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345618076 |
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| 245 | 1 | 0 | |a Functionally impaired isoforms regulate TMPRSS6 proteolytic activity |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Hepcidins |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Protein Isoforms |2 NLM | |
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| 700 | 1 | |a Désilets, Antoine |e verfasserin |4 aut | |
| 700 | 1 | |a Lemieux, Gabriel |e verfasserin |4 aut | |
| 700 | 1 | |a Leduc, Richard |e verfasserin |4 aut | |
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