Biochemical and Functional Characterization of the Three Zebrafish Transglutaminases 2

Manuel Lisetto, Mariagiulia Fattorini, Andrea Lanza, Marco Gerdol, Martin Griffin, Zhuo Wang, Fortunato Ferrara, Daniele Sblattero*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article number12041
Number of pages23
JournalInternational Journal of Molecular Sciences
Issue number15
Early online date27 Jul 2023
Publication statusPublished - 27 Jul 2023

Bibliographical note

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
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  • transglutaminase
  • zebrafish
  • cell adhesion
  • apoptosis
  • enzyme


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