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In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building

A disintegrin and metalloproteinase with thrombospondin type I motif (ADAMTS)2 and ADAMTS14 were originally known for their ability to cleave the aminopropeptides of fibrillar collagens. Previous work using N-terminomic approach (N-TAILS) in vitro led to the identification of new substrates, includi...

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Autores principales: Leduc, Cédric, Dupont, Laura, Joannes, Loïc, Monseur, Christine, Baiwir, Dominique, Mazzucchelli, Gabriel, Deroanne, Christophe, Colige, Alain, Bekhouche, Mourad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017238/
https://www.ncbi.nlm.nih.gov/pubmed/33816558
http://dx.doi.org/10.3389/fmolb.2021.643178
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author Leduc, Cédric
Dupont, Laura
Joannes, Loïc
Monseur, Christine
Baiwir, Dominique
Mazzucchelli, Gabriel
Deroanne, Christophe
Colige, Alain
Bekhouche, Mourad
author_facet Leduc, Cédric
Dupont, Laura
Joannes, Loïc
Monseur, Christine
Baiwir, Dominique
Mazzucchelli, Gabriel
Deroanne, Christophe
Colige, Alain
Bekhouche, Mourad
author_sort Leduc, Cédric
collection PubMed
description A disintegrin and metalloproteinase with thrombospondin type I motif (ADAMTS)2 and ADAMTS14 were originally known for their ability to cleave the aminopropeptides of fibrillar collagens. Previous work using N-terminomic approach (N-TAILS) in vitro led to the identification of new substrates, including some molecules involved in TGF-β signaling. Here, N-TAILS was used to investigate the substrates of these two enzymes in vivo, by comparing the N-terminomes of the skin of wild type mice, mice deficient in ADAMTS2, in ADAMTS14 and in both ADAMTS2 and ADAMTS14. This study identified 68 potential extracellular and cell surface proteins, with the majority of them being cleaved by both enzymes. These analyses comfort their role in collagen matrix organization and suggest their implication in inflammatory processes. Regarding fibrillar collagen, this study demonstrates that both ADAMTS2 and ADAMTS14 are involved in the processing of the aminopropeptide of alpha1 and alpha2 type V collagen. It also revealed the existence of several cleavage sites in the Col1 domain and in the C-propeptide of type I collagens. In addition to collagens and other extracellular proteins, two major components of the cell cytoskeleton, actin and vimentin, were also identified as potential substrates. The latter data were confirmed in vitro using purified enzymes and could potentially indicate other functions for ADAMTS2 and 14. This original investigation of mouse skin degradomes by N-terminomic highlights the essential role of ADAMTS2 and ADAMTS14 in collagen matrix synthesis and turnover, and gives clues to better understand their functions in skin pathophysiology. Data are available via ProteomeXchange with identifier PXD022179.
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spelling pubmed-80172382021-04-03 In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building Leduc, Cédric Dupont, Laura Joannes, Loïc Monseur, Christine Baiwir, Dominique Mazzucchelli, Gabriel Deroanne, Christophe Colige, Alain Bekhouche, Mourad Front Mol Biosci Molecular Biosciences A disintegrin and metalloproteinase with thrombospondin type I motif (ADAMTS)2 and ADAMTS14 were originally known for their ability to cleave the aminopropeptides of fibrillar collagens. Previous work using N-terminomic approach (N-TAILS) in vitro led to the identification of new substrates, including some molecules involved in TGF-β signaling. Here, N-TAILS was used to investigate the substrates of these two enzymes in vivo, by comparing the N-terminomes of the skin of wild type mice, mice deficient in ADAMTS2, in ADAMTS14 and in both ADAMTS2 and ADAMTS14. This study identified 68 potential extracellular and cell surface proteins, with the majority of them being cleaved by both enzymes. These analyses comfort their role in collagen matrix organization and suggest their implication in inflammatory processes. Regarding fibrillar collagen, this study demonstrates that both ADAMTS2 and ADAMTS14 are involved in the processing of the aminopropeptide of alpha1 and alpha2 type V collagen. It also revealed the existence of several cleavage sites in the Col1 domain and in the C-propeptide of type I collagens. In addition to collagens and other extracellular proteins, two major components of the cell cytoskeleton, actin and vimentin, were also identified as potential substrates. The latter data were confirmed in vitro using purified enzymes and could potentially indicate other functions for ADAMTS2 and 14. This original investigation of mouse skin degradomes by N-terminomic highlights the essential role of ADAMTS2 and ADAMTS14 in collagen matrix synthesis and turnover, and gives clues to better understand their functions in skin pathophysiology. Data are available via ProteomeXchange with identifier PXD022179. Frontiers Media S.A. 2021-03-19 /pmc/articles/PMC8017238/ /pubmed/33816558 http://dx.doi.org/10.3389/fmolb.2021.643178 Text en Copyright © 2021 Leduc, Dupont, Joannes, Monseur, Baiwir, Mazzucchelli, Deroanne, Colige and Bekhouche. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Leduc, Cédric
Dupont, Laura
Joannes, Loïc
Monseur, Christine
Baiwir, Dominique
Mazzucchelli, Gabriel
Deroanne, Christophe
Colige, Alain
Bekhouche, Mourad
In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building
title In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building
title_full In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building
title_fullStr In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building
title_full_unstemmed In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building
title_short In vivo N-Terminomics Highlights Novel Functions of ADAMTS2 and ADAMTS14 in Skin Collagen Matrix Building
title_sort in vivo n-terminomics highlights novel functions of adamts2 and adamts14 in skin collagen matrix building
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017238/
https://www.ncbi.nlm.nih.gov/pubmed/33816558
http://dx.doi.org/10.3389/fmolb.2021.643178
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