Functionally impaired isoforms regulate TMPRSS6 proteolytic activity.

Autor:	Sébastien P Dion, Antoine Désilets, Gabriel Lemieux, Richard Leduc
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	Medicine Science
Zdroj:	PLoS ONE, Vol 17, Iss 8, p e0273825 (2022)
Druh dokumentu:	article
ISSN:	1932-6203
DOI:	10.1371/journal.pone.0273825
Popis:	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.
Databáze:	Directory of Open Access Journals
Externí odkaz:	https://doaj.org/article/59be08b264514d2e81747bc264b43c0a Zobrazit plný text záznamu View record in DOAJ Plný text ve formátu PDF Plný text ve formátu HTML
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