Biochemical and Functional Characterization of the Three Zebrafish Transglutaminases 2

Abstract

Transglutaminase 2 (TG2) is a multifunctional protein widely distributed in various tissues and involved in many physiological and pathological processes. However, its actual role in biological processes is often controversial as TG2 shows different effects in these processes depending on its localization, cell type, or experimental conditions. We characterized the enzymatic and functional properties of TG2 proteins expressed in Danio rerio (zebrafish) to provide the basis for using this established animal model as a reliable tool to characterize TG2 functions in vivo. We confirmed the existence of three genes orthologous to human TG2 (zTGs2) in the zebrafish genome and their expression and function during embryonic development. We produced and purified the zTGs2s as recombinant proteins and showed that, like the human enzyme, zTGs2 catalyzes a Ca2+ dependent transamidation reaction that can be inhibited with TG2-specific inhibitors. In a cell model of human fibroblasts, we also demonstrated that zTGs2 can mediate RGD-independent cell adhesion in the extracellular environment. Finally, we transfected and selected zTGs2-overexpressing HEK293 cells and demonstrated that intracellular zTGs2 plays a very comparable protective/damaging role in the apoptotic process, as hTG2. Overall, our results suggest that zTGs2 proteins behave very similarly to the human ortholog and pave the way for future in vivo studies of TG2 functions in zebrafish.

Publication DOI: https://doi.org/10.3390/ijms241512041
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: Publisher Copyright: © 2023 by the authors. Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: transglutaminase,zebrafish,cell adhesion,apoptosis,enzyme
Publication ISSN: 1422-0067
Last Modified: 20 Jun 2024 07:32
Date Deposited: 05 Sep 2023 10:47
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.mdp ... 067/24/15/12041 (Publisher URL)
PURE Output Type: Article
Published Date: 2023-07-27
Published Online Date: 2023-07-27
Accepted Date: 2023-07-24
Authors: Lisetto, Manuel
Fattorini, Mariagiulia
Lanza, Andrea
Gerdol, Marco
Griffin, Martin (ORCID Profile 0000-0003-3824-306X)
Wang, Zhuo (ORCID Profile 0000-0002-2212-8318)
Ferrara, Fortunato
Sblattero, Daniele

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