Transcriptome analysis reveals TMPRSS6 isoforms with distinct functionalities
| Autor: | François Béliveau, Antoine Désilets, Mariana Gabriela Ghinet, Sébastien P. Dion, Richard Leduc |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene isoform TMPRSS6 media_common.quotation_subject serine protease Iron SMAD GPI-Linked Proteins IRIDA HJV Transcriptome 03 medical and health sciences Mice 0302 clinical medicine iron regulation matriptase‐2 Animals Homeostasis Humans Protein Isoforms Internalization Hemochromatosis Protein media_common Chemistry HEK 293 cells Serine Endopeptidases Membrane Proteins Cell Biology Original Articles Transmembrane protein Cell biology 030104 developmental biology HEK293 Cells Gene Expression Regulation 030220 oncology & carcinogenesis Molecular Medicine Original Article Heterologous expression hepcidin Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | TMPRSS6 (matriptase‐2) is a type II transmembrane serine protease involved in iron homoeostasis. At the cell surface of hepatocytes, TMPRSS6 cleaves haemojuvelin (HJV) and regulates the BMP/SMAD signalling pathway leading to production of hepcidin, a key regulator of iron absorption. Although four TMPRSS6 human isoforms and three mice Tmprss6 isoforms are annotated in databases (Ensembl and RefSeq), their relative expression or activity has not been studied. Analyses of RNA‐seq data and RT‐PCR from human tissues reveal that TMPRSS6 isoform 1 (TMPRSS6‐1) and 3 are mostly expressed in human testis while TMPRSS6‐2 and TMPRSS6‐4 are the main transcripts expressed in human liver, testis and pituitary. Furthermore, we confirm the existence and analyse the relative expression of three annotated mice Tmprss6 isoforms. Using heterologous expression in HEK293 and Hep3B cells, we show that all human TMPRSS6 isoforms reach the cell surface but only TMPRSS6‐1 undergoes internalization. Moreover, truncated TMPRSS6‐3 or catalytically altered TMPRSS6‐4 interact with HJV and prevent its cleavage by TMPRSS6‐2, suggesting their potential role as dominant negative isoforms. Taken together, our results highlight the importance of understanding the precise function of each TMPRSS6 isoforms both in human and in mouse. |
| Databáze: | OpenAIRE |
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