RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 and α5β1 integrin co-signaling

Zhuo Wang, Russell J Collighan, Stephane R Gross, Erik H. J. Danen, Gertraud Orend, Dilek Telci, Martin Griffin

Research output: Contribution to journalArticle

Abstract

Fibronectin (FN) deposition mediated by fibroblasts is an important process in matrix remodeling and wound healing. By monitoring the deposition of soluble biotinylated FN, we show that the stress-induced TG-FN matrix, a matrix complex of tissue transglutaminase (TG2) with its high affinity binding partner FN, can increase both exogenous and cellular FN deposition and also restore it when cell adhesion is interrupted via the presence of RGD-containing peptides. This mechanism does not require the transamidase activity of TG2 but is activated through an RGD-independent adhesion process requiring a heterocomplex of TG2 and FN and is mediated by a syndecan-4 and ß1 integrin co-signaling pathway. By using a5 null cells, ß1 integrin functional blocking antibody, and a a5ß1 integrin targeting peptide A5-1, we demonstrate that the a5 and ß1 integrins are essential for TG-FN to compensate RGD-induced loss of cell adhesion and FN deposition. The importance of syndecan-2 in this process was shown using targeting siRNAs, which abolished the compensation effect of TG-FN on the RGD-induced loss of cell adhesion, resulting in disruption of actin skeleton formation and FN deposition. Unlike syndecan-4, syndecan-2 does not interact directly with TG2 but acts as a downstream effector in regulating actin cytoskeleton organization through the ROCK pathway. We demonstrate that PKCa is likely to be the important link between syndecan-4 and syndecan-2 signaling and that TG2 is the functional component of the TG-FN heterocomplex in mediating cell adhesion via its direct interaction with heparan sulfate chains.
LanguageEnglish
Pages40212-40129
Number of pages18
JournalJournal of Biological Chemistry
Volume285
Issue number51
Early online date7 Oct 2010
DOIs
Publication statusPublished - 17 Dec 2010

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Syndecan-2
Syndecan-4
Cell adhesion
Fibronectins
Cell Adhesion
Integrins
Actins
transglutaminase 2
Null Lymphocytes
Blocking Antibodies
Heparitin Sulfate
Fibroblasts
Actin Cytoskeleton
Skeleton
Wound Healing

Bibliographical note

© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Keywords

  • actins
  • animals
  • CHO cells
  • cell adhesion
  • cricetinae
  • cricetulus
  • cytoskeleton
  • extracellular matrix
  • fibronectins
  • GTP-binding proteins
  • heparitin sulfate
  • humans
  • integrin alpha5beta1
  • mice
  • mutant strains mice
  • oligopeptides
  • protein kinase C-alpha
  • Small Interfering RNA
  • signal transduction
  • syndecan-2
  • syndecan-4
  • transglutaminases
  • rho-associated kinases

Cite this

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title = "RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 and α5β1 integrin co-signaling",
abstract = "Fibronectin (FN) deposition mediated by fibroblasts is an important process in matrix remodeling and wound healing. By monitoring the deposition of soluble biotinylated FN, we show that the stress-induced TG-FN matrix, a matrix complex of tissue transglutaminase (TG2) with its high affinity binding partner FN, can increase both exogenous and cellular FN deposition and also restore it when cell adhesion is interrupted via the presence of RGD-containing peptides. This mechanism does not require the transamidase activity of TG2 but is activated through an RGD-independent adhesion process requiring a heterocomplex of TG2 and FN and is mediated by a syndecan-4 and {\ss}1 integrin co-signaling pathway. By using a5 null cells, {\ss}1 integrin functional blocking antibody, and a a5{\ss}1 integrin targeting peptide A5-1, we demonstrate that the a5 and {\ss}1 integrins are essential for TG-FN to compensate RGD-induced loss of cell adhesion and FN deposition. The importance of syndecan-2 in this process was shown using targeting siRNAs, which abolished the compensation effect of TG-FN on the RGD-induced loss of cell adhesion, resulting in disruption of actin skeleton formation and FN deposition. Unlike syndecan-4, syndecan-2 does not interact directly with TG2 but acts as a downstream effector in regulating actin cytoskeleton organization through the ROCK pathway. We demonstrate that PKCa is likely to be the important link between syndecan-4 and syndecan-2 signaling and that TG2 is the functional component of the TG-FN heterocomplex in mediating cell adhesion via its direct interaction with heparan sulfate chains.",
keywords = "actins, animals, CHO cells, cell adhesion, cricetinae, cricetulus, cytoskeleton, extracellular matrix, fibronectins, GTP-binding proteins, heparitin sulfate, humans, integrin alpha5beta1, mice, mutant strains mice, oligopeptides, protein kinase C-alpha, Small Interfering RNA, signal transduction, syndecan-2, syndecan-4, transglutaminases, rho-associated kinases",
author = "Zhuo Wang and Collighan, {Russell J} and Gross, {Stephane R} and Danen, {Erik H. J.} and Gertraud Orend and Dilek Telci and Martin Griffin",
note = "{\circledC} 2010 by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2010",
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TY - JOUR

T1 - RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 and α5β1 integrin co-signaling

AU - Wang, Zhuo

AU - Collighan, Russell J

AU - Gross, Stephane R

AU - Danen, Erik H. J.

AU - Orend, Gertraud

AU - Telci, Dilek

AU - Griffin, Martin

N1 - © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2010/12/17

Y1 - 2010/12/17

N2 - Fibronectin (FN) deposition mediated by fibroblasts is an important process in matrix remodeling and wound healing. By monitoring the deposition of soluble biotinylated FN, we show that the stress-induced TG-FN matrix, a matrix complex of tissue transglutaminase (TG2) with its high affinity binding partner FN, can increase both exogenous and cellular FN deposition and also restore it when cell adhesion is interrupted via the presence of RGD-containing peptides. This mechanism does not require the transamidase activity of TG2 but is activated through an RGD-independent adhesion process requiring a heterocomplex of TG2 and FN and is mediated by a syndecan-4 and ß1 integrin co-signaling pathway. By using a5 null cells, ß1 integrin functional blocking antibody, and a a5ß1 integrin targeting peptide A5-1, we demonstrate that the a5 and ß1 integrins are essential for TG-FN to compensate RGD-induced loss of cell adhesion and FN deposition. The importance of syndecan-2 in this process was shown using targeting siRNAs, which abolished the compensation effect of TG-FN on the RGD-induced loss of cell adhesion, resulting in disruption of actin skeleton formation and FN deposition. Unlike syndecan-4, syndecan-2 does not interact directly with TG2 but acts as a downstream effector in regulating actin cytoskeleton organization through the ROCK pathway. We demonstrate that PKCa is likely to be the important link between syndecan-4 and syndecan-2 signaling and that TG2 is the functional component of the TG-FN heterocomplex in mediating cell adhesion via its direct interaction with heparan sulfate chains.

AB - Fibronectin (FN) deposition mediated by fibroblasts is an important process in matrix remodeling and wound healing. By monitoring the deposition of soluble biotinylated FN, we show that the stress-induced TG-FN matrix, a matrix complex of tissue transglutaminase (TG2) with its high affinity binding partner FN, can increase both exogenous and cellular FN deposition and also restore it when cell adhesion is interrupted via the presence of RGD-containing peptides. This mechanism does not require the transamidase activity of TG2 but is activated through an RGD-independent adhesion process requiring a heterocomplex of TG2 and FN and is mediated by a syndecan-4 and ß1 integrin co-signaling pathway. By using a5 null cells, ß1 integrin functional blocking antibody, and a a5ß1 integrin targeting peptide A5-1, we demonstrate that the a5 and ß1 integrins are essential for TG-FN to compensate RGD-induced loss of cell adhesion and FN deposition. The importance of syndecan-2 in this process was shown using targeting siRNAs, which abolished the compensation effect of TG-FN on the RGD-induced loss of cell adhesion, resulting in disruption of actin skeleton formation and FN deposition. Unlike syndecan-4, syndecan-2 does not interact directly with TG2 but acts as a downstream effector in regulating actin cytoskeleton organization through the ROCK pathway. We demonstrate that PKCa is likely to be the important link between syndecan-4 and syndecan-2 signaling and that TG2 is the functional component of the TG-FN heterocomplex in mediating cell adhesion via its direct interaction with heparan sulfate chains.

KW - actins

KW - animals

KW - CHO cells

KW - cell adhesion

KW - cricetinae

KW - cricetulus

KW - cytoskeleton

KW - extracellular matrix

KW - fibronectins

KW - GTP-binding proteins

KW - heparitin sulfate

KW - humans

KW - integrin alpha5beta1

KW - mice

KW - mutant strains mice

KW - oligopeptides

KW - protein kinase C-alpha

KW - Small Interfering RNA

KW - signal transduction

KW - syndecan-2

KW - syndecan-4

KW - transglutaminases

KW - rho-associated kinases

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U2 - 10.1074/jbc.M110.123703

DO - 10.1074/jbc.M110.123703

M3 - Article

VL - 285

SP - 40212

EP - 40129

JO - Journal of Biological Chemistry

T2 - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 51

ER -