A novel RGD-independent cel adhesion pathway mediated by fibronectin-bound tissue transglutaminase rescues cells from anoikis

Elisabetta A.M. Verderio, Dilek Telci, Afam Okoye, Gerry Melino, Martin Griffin

Research output: Contribution to journalArticle

Abstract

Specific association of tissue transglutaminase (tTG) with matrix fibronectin (FN) results in the formation of an extracellular complex (tTG-FN) with distinct adhesive and pro-survival characteristics. tTG-FN supports RGD-independent cell adhesion of different cell types and the formation of distinctive RhoA-dependent focal adhesions following inhibition of integrin function by competitive RGD peptides and function blocking anti-integrin antibodies alpha5beta1. Association of tTG with its binding site on the 70-kDa amino-terminal FN fragment does not support this cell adhesion process, which seems to involve the entire FN molecule. RGD-independent cell adhesion to tTG-FN does not require transamidating activity, is mediated by the binding of tTG to cell-surface heparan sulfate chains, is dependent on the function of protein kinase Calpha, and leads to activation of the cell survival focal adhesion kinase. The tTG-FN complex can maintain cell viability of tTG-null mouse dermal fibroblasts when apoptosis is induced by inhibition of RGD-dependent adhesion (anoikis), suggesting an extracellular survival role for tTG. We propose a novel RGD-independent cell adhesion mechanism that promotes cell survival when the anti-apoptotic role mediated by RGD-dependent integrin function is reduced as in tissue injury, which is consistent with the externalization and binding of tTG to fibronectin following cell damage/stress.
Original languageEnglish
Pages (from-to)42604-42614
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number43
DOIs
Publication statusPublished - 24 Oct 2003

Bibliographical note

© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

Keywords

  • 3T3 cells
  • animals
  • anoikis
  • cell adhesion
  • cultured cells
  • cytoskeleton
  • fibroblasts
  • fibronectins
  • focal adhesions
  • guinea pigs
  • heparin
  • humans
  • mice
  • oligopeptides
  • osteoblasts
  • protein binding
  • protein kinase C
  • protein kinase C-alpha
  • proteoglycans
  • transglutaminases

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