Vitronectin's Basic Domain is a Syndecan Ligand which Functions in trans to Regulate Vitronectin Turnover

Wilkins-Port, Cynthia E.; Sanderson, Ralph D.; Tominna-Sebald, Eiman; McKeown‐Longo, Paula J.

doi:10.1080/714040415

Cited by 9 publications

(13 citation statements)

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“…However, providing trace amounts of VN or FN to B82L cells already anchored to a Sdc1 antibody reveals an integrin-related activity of the syndecan, namely, extensive cell spreading via syndecan-regulated signaling of the ␣ v ␤ 5 integrin. These data might help explain the apparent link between Sdc1 and ␣ v ␤ 5 -dependent turnover of VN (Wilkins-Port et al, 2003). The regulation of integrin activity by Sdc1 might occur either by altering integrin activation and/or by altering integrin signaling in response to the ligand (i.e.…”

Section: Discussionmentioning

confidence: 99%

Syndecan-1 regulates αvβ5 integrin activity in B82L fibroblasts

McQuade

Beauvais

Burbach

et al. 2006

Journal of Cell Science

102

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B82L mouse fibroblasts respond to fibronectin or vitronectin via a syndecan-1-mediated activation of the αvβ5 integrin. Cells attached to syndecan-1-specific antibody display only filopodial extension. However, the syndecan-anchored cells extend lamellipodia when the antibody-substratum is supplemented with serum, or low concentrations of adsorbed vitronectin or fibronectin, that are not sufficient to activate the integrin when plated alone. Integrin activation is blocked by treatment with (Arg-Gly-Asp)-containing peptides and function-blocking antibodies that target αv integrins, as well as by siRNA-mediated silencing of β5 integrin expression. In addition, αvβ5-mediated cell attachment and spreading on high concentrations of vitronectin is blocked by competition with recombinant syndecan-1 ectodomain core protein and by downregulation of mouse syndecan-1 expression by mouse-specific siRNA. Taking advantage of the species-specificity of the siRNA, rescue experiments in which human syndecan-1 constructs are expressed trace the activation site to the syndecan-1 ectodomain. Moreover, both full-length mouse and human syndecan-1 co-immunoprecipitate with the β5 integrin subunit, but fail to do so if the syndecan is displaced by competition with soluble, recombinant syndecan-1 ectodomain. These results suggest that the ectodomain of the syndecan-1 core protein contains an active site that assembles into a complex with the αvβ5 integrin and regulates αvβ5 integrin activity.

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Section: Discussionmentioning

confidence: 99%

Syndecan-1 regulates αvβ5 integrin activity in B82L fibroblasts

McQuade

Beauvais

Burbach

et al. 2006

Journal of Cell Science

102

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“…The lack of post-translational modifications is one of the potential drawbacks in using these systems, especially with a protein like vitronectin that has numerous post-translational modifications, including disulfide bonds. The baculovirus system was chosen for expression of the vitronectin deletion mutant lacking the somatomedin B domain, because this system has been used successfully to express vitronectin (41,52,63,64). Characterization of full-length vitronectin produced by the baculovirus cells determined it to be functionally similar to multimeric vitronectin (41).…”

Section: A Mutant Form Of Vitronectin Lacking the Somatomedin B Domaimentioning

confidence: 99%

A Deletion Mutant of Vitronectin Lacking the Somatomedin B Domain Exhibits Residual Plasminogen Activator Inhibitor-1-binding Activity

Schar

Blouse

Minor

et al. 2008

Journal of Biological Chemistry

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Vitronectin and plasminogen activator inhibitor-1 (PAI-1) are important physiological binding partners that work in concert to regulate cellular adhesion, migration, and fibrinolysis. The high affinity binding site for PAI-1 is located within the N-terminal somatomedin B domain of vitronectin; however, several studies have suggested a second PAI-1-binding site within vitronectin. To investigate this secondary site, a vitronectin mutant lacking the somatomedin B domain (r⌬sBVN) was engineered. The short deletion had no effect on heparin-binding, integrin-binding, or cellular adhesion. Binding to the urokinase receptor was completely abolished while PAI-1 binding was still observed, albeit with a lower affinity. Analytical ultracentrifugation on the PAI-1-vitronectin complex demonstrated that increasing NaCl concentration favors 1:1 versus 2:1 PAI-1-vitronectin complexes and hampers formation of higher order complexes, pointing to the contribution of charge-charge interactions for PAI-1 binding to the second site. Furthermore, fluorescence resonance energy transfer between differentially labeled PAI-1 molecules confirmed that two independent molecules of PAI-1 are capable of binding to vitronectin. These results support a model for the assembly of higher order PAI-1-vitronectin complexes via two distinct binding sites in both proteins.

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“…Modulation by fibulin-1 also requires FN and syndecan-4. In contrast, vitronectin, which binds syndecan-4 (Wilkins-Port and Mckeown-Longo, 1996;Wilkins-Port et al, 2003) and fibrin (Podor et al, 2001), did not affect fibroblast adhesion and spreading on a fibrin-FN matrix. This result indicates that fibrin and syndecan-4 interactions are not sufficient to modulate adhesion in this system.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, like tenascin-C, fibulin-1 binds to the HepII domain (Balbona et al, 1992) and has been shown to have cell adhesion-and motility-suppressive effects on FN-coated substrates (Twal et al, 2001). Vitronectin, in contrast, binds to syndecans (Wilkins-Port and Mckeown-Longo, 1996;Wilkins-Port et al, 2003) but not to FN. This raises the question whether these proteins modulate adhesion by FN-or syndecan-dependent interactions.…”

Section: Introductionmentioning

confidence: 99%

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A Shared Mechanism of Adhesion Modulation for Tenascin-C and Fibulin-1

Williams

Schwarzbauer

2009

MBoC

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Adhesion modulatory proteins are important effectors of cell-matrix interactions during tissue remodeling and regeneration. They comprise a diverse group of matricellular proteins that confer antiadhesive properties to the extracellular matrix (ECM). We compared the inhibitory effects of two adhesion modulatory proteins, fibulin-1 and tenascin-C, both of which bind to the C-terminal heparin-binding (HepII) domain of fibronectin (FN) but are structurally distinct. Here, we report that, like tenascin-C, fibulin-1 inhibits fibroblast spreading and cell-mediated contraction of a fibrin-FN matrix. These proteins act by modulation of focal adhesion kinase and extracellular signal-regulated kinase signaling. The inhibitory effects were bypassed by lysophosphatidic acid, an activator of RhoA GTPase. Fibroblast response to fibulin-1, similar to tenascin-C, was dependent on expression of the heparan sulfate proteoglycan syndecan-4, which also binds to the HepII domain. Therefore, blockade of HepII-mediated signaling by competitive binding of fibulin-1 or tenascin-C represents a shared mechanism of adhesion modulation among disparate modulatory proteins. INTRODUCTIONTissue architecture is determined by positioning of cells within the fibrillar assemblage of proteins, proteoglycans, and other components that comprise the extracellular matrix (ECM). Organization and composition of the ECM have significant impacts on many cellular functions. By binding to transmembrane receptors, individual ECM components affect cell arrangements and initiate signaling events that alter gene expression and regulate cell communication. Fibronectin (FN) is a ubiquitously expressed, multifunctional ECM glycoprotein that promotes cell adhesion and plays important roles in tissue development, repair, and remodeling (Hynes, 1990). Cell interactions with FN are largely dependent on integrin receptors with subsequent engagement of intracellular signaling and cytoskeletal components (Hynes, 2002). Tissue development and remodeling require changes in cell adhesion to allow cell proliferation, cell motility, and ECM reorganization (Singer and Clark, 1999). Modulation of cell adhesion can be achieved by modifications in FN matrix organization or composition (Sechler et al., 1998;Midwood et al., 2006) or by the deposition of adhesion modulatory or matricellular proteins (Bornstein and Sage, 2002), including tenascin-C, fibulin-1, thrombospondin-1 (TSP-1), and many others (Fassler et al., 1996;Bornstein, 2001;Chiquet-Ehrismann and Chiquet, 2003;Midwood et al., 2004b).Expression of proteins that modulate cell adhesion causes reduced cell interactions with adhesive ECM, thus allowing cell movement, shape changes, proliferation, and other related processes (Chiquet-Ehrismann, 1991;Orend and Chiquet-Ehrismann, 2000). The suppression of adhesion-related signal transduction produces dramatic changes in cytoskeletal organization and in the kinetics of cell contact with the ECM. Adhesion modulatory proteins comprise an increasingly diverse group, suggesting that t...

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Vitronectin's Basic Domain is a Syndecan Ligand which Functions in trans to Regulate Vitronectin Turnover

Cited by 9 publications

References 0 publications

Syndecan-1 regulates αvβ5 integrin activity in B82L fibroblasts

Syndecan-1 regulates αvβ5 integrin activity in B82L fibroblasts

A Deletion Mutant of Vitronectin Lacking the Somatomedin B Domain Exhibits Residual Plasminogen Activator Inhibitor-1-binding Activity

A Shared Mechanism of Adhesion Modulation for Tenascin-C and Fibulin-1

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