Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells

Maria Felicia Soluri, Francesca Boccafoschi, Diego Cotella, Laura Moro, Gabriela Forestieri, Ida Autiero, Luigi Cavallo, Romina Oliva, Martin Griffin, Zhuo Wang, Claudio Santoro, Daniele Sblattero

Research output: Contribution to journalArticle

Abstract

The interaction between the enzyme transglutaminase 2 (TG2) and fibronectin (FN) is involved in the cellmatrix interactions that regulate cell signaling, adhesion, and migration and play central roles in pathologic conditions, particularly fibrosisandcancer.Aprecisedefinitionof the exact interactiondomainsonboth proteins couldprovide a tool to design novelmolecules with potential therapeutic applications.Although specific residues involved in the interaction within TG2 have been analyzed, little is known regarding the TG2 binding site on FN. This site has been mapped to a large internal 45-kDa protein fragment coincident with the gelatin binding domain (GBD). With the goal of defining the minimal FN interacting domain for TG2, we produced several expression constructs encoding different portions or modules of the GBD and tested their binding and functional properties. The results demonstrate that the I8 module is necessary and sufficient forTG2-binding in vitro, but does not have functional effects on TG2-expressing cells.Modules I7 and I9 increase the strength of the binding and are required for cell adhesion. A 15-kDa fragment encompassing modules I7-9 behaves as the whole 45-kDa GBD and mediates signaling, adhesion, spreading, and migration of TG2 + cells.Thisstudy providesnewinsights into themechanismforTG2binding toFN.

Original languageEnglish
Pages (from-to)2327-2342
Number of pages16
JournalFASEB Journal
Volume33
Issue number2
Early online date4 Oct 2018
DOIs
Publication statusPublished - 30 Jan 2019

Keywords

  • cell adhesion
  • extracellular matrix
  • gelatin binding domain (GBD)
  • ovarian cancer

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