Quantitative Proteomics Reveals Changes Induced by TIMP-3 on Cell Membrane Composition and Novel Metalloprotease Substrates
| Autor: | Simone Bonelli, Veronica M. Pravata, Stefan F. Lichtenthaler, Elisa Monaca, Matteo Calligaris, Danilo D'Apolito, Stephan A. Müller, Anna Paola Carreca, Simone D. Scilabra |
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| Přispěvatelé: | Anna Paola Carreca, Veronica Maria Pravatà, Danilo D'Apolito, Simone Bonelli, Matteo Calligaris, Elisa Monaca, Stephan A Müller, Stefan F Lichtenthaler, Simone Dario Scilabra |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Proteomics ADAM15 Proteome Cell Matrix metalloproteinase Mass Spectrometry Cell membrane lcsh:Chemistry analysis [Proteome] lcsh:QH301-705.5 proteomic Spectroscopy biology Chemistry tissue inhibitor of metalloproteases 3 (TIMP-3) General Medicine Transmembrane protein Computer Science Applications Cell biology medicine.anatomical_structure Ectodomain ddc:540 TIMP3 protein human metalloproteinase ectodomain shedding metabolism [Tissue Inhibitor of Metalloproteinase-3] Quantitative proteomics ADAM15 protein human chemistry [Cell Membrane] Catalysis metabolism [Cell Membrane] Article metalloproteinases Inorganic Chemistry 03 medical and health sciences medicine Disintegrin Humans Physical and Theoretical Chemistry Molecular Biology Tissue Inhibitor of Metalloproteinase-3 030102 biochemistry & molecular biology Organic Chemistry Cell Membrane Membrane Proteins metabolism [Proteome] ADAM Proteins 030104 developmental biology HEK293 Cells lcsh:Biology (General) lcsh:QD1-999 metabolism [ADAM Proteins] biology.protein metabolism [Membrane Proteins] |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 5 International Journal of Molecular Sciences, Vol 22, Iss 2392, p 2392 (2021) International journal of molecular sciences 22(5), 2392-(2021). doi:10.3390/ijms22052392 |
| ISSN: | 1422-0067 |
| Popis: | Ectodomain shedding is a key mechanism of several biological processes, including cell-communication. Disintegrin and metalloproteinases (ADAMs), together with the membrane-type matrix metalloproteinases, play a pivotal role in shedding transmembrane proteins. Aberrant shedding is associated to several pathological conditions, including arthritis. Tissue inhibitor of metalloproteases 3 (TIMP-3), an endogenous inhibitor of ADAMs and matrix metalloproteases (MMPs), has been proven to be beneficial in such diseases. Thus, strategies to increase TIMP-3 bioavailability in the tissue have been sought for development of therapeutics. Nevertheless, high levels of TIMP-3 may lead to mechanism-based side-effects, as its overall effects on cell behavior are still unknown. In this study, we used a high-resolution mass-spectrometry-based workflow to analyze alterations induced by sustained expression of TIMP-3 in the cell surfaceome. In agreement with its multifunctional properties, TIMP-3 induced changes on the protein composition of the cell surface. We found that TIMP-3 had differential effects on metalloproteinase substrates, with several that accumulated in TIMP-3-overexpressing cells. In addition, our study identified potentially novel ADAM substrates, including ADAM15, whose levels at the cell surface are regulated by the inhibitor. In conclusion, our study reveals that high levels of TIMP-3 induce modifications in the cell surfaceome and identifies molecular pathways that can be deregulated via TIMP-3-based therapies. |
| Databáze: | OpenAIRE |
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